Potentially preventable hospitalisations in rural community-dwelling patients.

BACKGROUND: Potentially preventable hospitalisations (PPH) are a common occurrence. Knowing the factors associated with PPH may allow high-risk patients to be identified and healthcare resources to be better allocated, and these factors may differ between urban and rural locations. AIM: To determine factors associated with PPH in an Australian rural population. METHODS: A retrospective review of admitted patients' demographic and clinical data was used to describe and model the factors associated with PPH, using an age- and sex-matched control group of non-admitted patients. This study is based in a multi-site rural general practice, Tasmania. The study included patients aged ≥18 years residing in the Huon-Bruny Island region of Tasmania, who were active patients at a rural general practice and were admitted to a public hospital for a PPH between 1 July 2016 and 30 June 2019. Main outcome measure is overnight admission to hospital for a PPH. RESULTS: Predictors with a significant odds ratio (OR) in the final model were being single/unmarried (OR 2.43; 95% confidence interval (CI) 1.38-4.28), higher Charlson Comorbidity Index score (OR 1.40; 95% CI 1.13-1.74) and the number of general practice visits in the preceding 12 months (OR 1.09; 95% CI 1.05-1.14). CONCLUSIONS: This study found that being single and having a higher comorbidity burden were the strongest independent risk factors for PPH in a rural population. Demographic and socioeconomic factors appeared to be as, if not more, important than medical factors and warrant attention when considering the design of programmes to reduce PPH risk in rural communities.

Impact of pharmacist interventions provided in the emergency department on quality use of medicines: a systematic review and meta-analysis.

BACKGROUND: Pharmacists have an increasing role as part of the emergency department (ED) team. However, the impact of ED-based pharmacy interventions on the quality use of medicines has not been well characterised. OBJECTIVE: This systematic review aimed to synthesise evidence from studies examining the impact of interventions provided by pharmacists on the quality use of medicines in adults presenting to ED. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE and CINAHL. Two independent reviewers screened titles/abstracts and reviewed full texts. Studies that compared the impact of interventions provided by pharmacists with usual care in ED and reported medication-related primary outcomes were included. Cochrane Risk of Bias-2 and Newcastle-Ottawa tools were used to assess the risk of bias. Summary estimates were pooled using random-effects meta-analysis, along with sensitivity and sub-group analyses. RESULTS: Thirty-one studies involving 13 242 participants were included. Pharmacists were predominantly involved in comprehensive medication review, advanced pharmacotherapy assessment, staff and patient education, identification of medication discrepancies and drug-related problems, medication prescribing and co-prescribing, and medication preparation and administration. The activities reduced the number of medication errors by a mean of 0.33 per patient (95% CI -0.42 to -0.23, I2=51%) and the proportion of patients with at least one error by 73% (risk ratio (RR)=0.27, 95% CI 0.19 to 0.40, I2=85.3%). The interventions were also associated with more complete and accurate medication histories, increased appropriateness of prescribed medications by 58% (RR=1.58, 95% CI 1.21 to 2.06, I2=95%) and quicker initiation of time-critical medications. CONCLUSION: The evidence indicates improved quality use of medicines when pharmacists are included in ED care teams. PROSPERO REGISTRATION NUMBER: CRD42020165234.

Switching of oral anticoagulants in patients with nonvalvular atrial fibrillation: A narrative review.

Approval of direct-acting oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF) was an important milestone, providing a wider range of treatment options and creating the possibility for drug switching after initiation. In addition to improved utilisation of oral anticoagulants (OACs) for stroke prevention, reports of switching among OACs are growing in the literature; switching may influence clinical outcomes, healthcare costs and patient satisfaction. This review aimed to summarise the current literature on the pattern of OAC switching in patients with AF, including reasons for switching and clinical consequences following switching. A literature search was conducted in PubMed, Scopus and Embase on 27 June 2020. We included 39 articles published after 2013, following the introduction of apixaban. The review found that switching among OACs was common in clinical practice, significantly varying with the type of OAC. Studies reporting the reason for switching and clinical outcomes were comparatively limited. The decision to switch was often related to safety issues (usually bleeding), poor anticoagulation control and ease of use. Patient characteristics, clinical conditions and drug interactions were found to be associated with switching from OACs. Findings regarding bleeding outcomes following switching were inconsistent, possibly confounded by the rationale for switching and the switching protocol. Noting the limited number of studies included and their relatively short follow-up periods, switching did not have a significant impact on the risk of stroke and other thrombotic outcomes. Further prospective studies are needed to understand better potential rationales for switching and the clinical outcomes.

Efficacy and safety of remdesivir in hospitalised COVID-19 patients: a systematic review and meta-analysis.

PURPOSE: This review was aimed to synthesise the best available evidence on the effectiveness and safety of remdesivir in the treatment of moderate to severe COVID-19. METHOD: Randomised controlled trials (RCTs) and observational studies reporting the effectiveness and safety of remdesivir were searched via databases and other sources from December 2019 to December 2020. Two independent reviewers performed literature screening, data extraction and assessment of risk bias. Seven studies involving 3686 patients were included. RESULTS: Treatment with remdesivir was associated with an increase in clinical recovery rate by 21% (RR 1.21; 95% CI 1.08-1.35) on day 7 and 29% (RR 1.29; 95% CI 1.22-1.37) on day 14. The likelihoods of requiring high-flow supplemental oxygen and invasive mechanical ventilation in the remdesivir group were lower than in the placebo group by 27% (RR 0.73; 95% CI 0.54-0.99) and 47% (RR 0.53; 95% CI 0.39-0.72), respectively. Remdesivir-treated patients showed a 39% (RR 0.61; 95% CI 0.46-0.79) reduction in the risk of mortality on day 14 compared to the control group; however, there was no significant difference on day 28. Serious adverse effects (SAEs) were significantly less common in patients treated with remdesivir, with an absolute risk difference of 6% (RD -0.06; 95% CI -0.09 to -0.03). CONCLUSION: Despite conditional recommendation against its use, remdesivir could still be effective in early clinical improvement; reduction of early mortality and avoiding high-flow supplemental oxygen and invasive mechanical ventilation among hospitalised COVID-19 patients. Remdesivir was also well tolerated without significant SAEs compared to placebo, yet available evidence from clinical studies support the need to conduct close monitoring.

The global prevalence and trend of human intestinal carriage of ESBL-producing Escherichia coli in the community.

OBJECTIVES: Intestinal colonization by ESBL Escherichia coli and its association with community-acquired MDR infections is of great concern. This review determined the worldwide prevalence of human faecal ESBL E. coli carriage and its trend in the community over the past two decades. METHODS: A systematic literature search was conducted using PubMed, EMBASE and Google Scholar to retrieve articles published between 1 January 2000 and 13 February 2020 that contained data on the prevalence of faecal carriage of ESBL E. coli among healthy individuals. A cumulative (for the whole period) meta-analysis was used to estimate the global and regional pooled prevalence rates. Articles were grouped into study periods of 3 years, and subgroup meta-analyses were undertaken to examine the global pooled prevalence over time. RESULTS: Sixty-two articles covering 29 872 healthy persons were included in this meta-analysis. The cumulative (2003-18) global pooled prevalence of ESBL E. coli intestinal carriage in the community was 16.5% (95% CI 14.3%-18.7%; P  <  0.001). The pooled prevalence showed an upward trend, increasing from 2.6% (95% CI 1.6%-4.0%) in 2003-05 to 21.1% (95% CI 15.8%-27.0%) in 2015-18. Over the whole period, the highest carriage rate was observed in South-East Asia (27%; 95% CI 2.9%-51.3%), while the lowest occurred in Europe (6.0%; 95% CI 4.6%-7.5%). CONCLUSIONS: Globally, an 8-fold increase in the intestinal carriage rate of ESBL E. coli in the community has occurred over the past two decades. Prevention of its spread may require new therapeutic and public health strategies.

Variation in the pharmacokinetics of glucosamine in healthy individuals.

OBJECTIVES: Clinical trial data for the efficacy of glucosamine in OA are conflicting. Reportedly, Rotta-manufactured glucosamine products are more likely to be effective, and a possible explanation is greater bioavailability than other brands. Specifically, the aim was to compare the steady-state pharmacokinetics of Rotta- and non-Rotta-manufactured glucosamine products in healthy volunteers and examine the interindividual variability. METHODS: In a crossover design, healthy adult participants ingested 1500 mg/day of a Rotta (DONA powder sachets; imported by Mylan Health, Carole Park, QLD, Australia) and a non-Rotta (glucosamine sulphate 1500 mg one-a-day tablet; Blackmores, Warriewood, NSW, Australia) glucosamine product/brand individually for 6 days. Blood samples were collected immediately before and for 12 h after the ingestion of the last dose of each brand and analysed to determine plasma levels of glucosamine. The pharmacokinetic parameters at steady state [including the minimum (Css min) and maximum (Css max) plasma concentration of glucosamine, time to reach Css max post-dosing (Tss max) and area under the plasma concentration vs time curve (AUCss 0-12)] for each brand were calculated and statistically compared. RESULTS: Fourteen participants [mean age 35.5 years (s.d. 8.8)] were recruited (64.2% males). No significant differences were observed in the pharmacokinetic parameters between the two brands. However, for both brands, the coefficient of variation for Css min, Tss max and AUCss 0-12 exceeded 20%, indicating considerable differences in the parameters between participants. No significant association of the pharmacokinetic parameters was observed with various dosing- and participant-related variables. CONCLUSION: Substantial interindividual differences in the absorption and elimination of glucosamine could be a cause of variable clinical outcomes in OA. TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry (http://www.ANZCTR.org.au/ACTRN12618000699268p.aspx), number ACTRN12618000699268p.

Stroke risk reassessment and oral anticoagulant initiation in primary care patients with atrial fibrillation: A ten-year follow-up.

AIM: To examine the change in stroke risk over time and determine the proportion of patients with atrial fibrillation (AF) who were initiated on an oral anticoagulant (OAC) as their stroke risk increased from low/moderate to high, using the Australian general practice data set, MedicineInsight. METHODS: A total of 2296 patients diagnosed with AF between 1 January 2007 and 31 December 2008, aged 18 years or older and not initiated on an OAC before 2009, were included. We assessed the change in stroke risk and the proportion of patients who had a recorded prescription of an OAC, each year from 1 January 2009 to 31 December 2018. RESULTS: At baseline, 23.9%, 22.9% and 53.2% were categorised as being at low (score = 0), moderate (score = 1) and high stroke risk (score ≥ 2), respectively, using the sexless CHA2 DS2 -VASc (CHA2 DS2 -VA) score. Overall, the CHA2 DS2 -VA score increased by a mean of 1.34 (95% confidence interval, 1.29-1.39) points over the study period. Nearly two-thirds of patients (65%, 412/632) whose stroke risk changed from baseline low/moderate to high were subsequently prescribed an OAC. The median (interquartile range) lag time from becoming high stroke risk to having OAC initiation was 2 (5) years. CONCLUSIONS: Nearly one-third of patients reclassified as being at high risk of stroke during the study period were not prescribed OAC therapy. Furthermore, the delay in OAC initiation following classification as being at high risk was a median of 2 years, suggesting that more frequent stroke reassessment is needed.

Factors influencing oral anticoagulant use in patients newly diagnosed with atrial fibrillation.

BACKGROUND: We investigated factors that influenced oral anticoagulant (OAC) initiation and choice in Australian general practice patients newly diagnosed with AF. METHODS: Using an Australian nationally representative general practice dataset, MedicineInsight, we identified patients newly diagnosed with AF between January 2009 and April 2019. Logistic regression analyses were used to examine factors associated with OAC initiation and choice. RESULTS: A total of 63 212 patients with AF (53.7% males, mean age 72.4 years) were identified. Nearly two-thirds of these patients (40 854 [64.6%]) were initiated on an OAC, at a median time of 6 days after the documented diagnosis date. The proportion of patients who were initiated an OAC increased from 44.8% in 2009 to 72.2% in 2019 (P < .001). High risk of stroke (CHA2 DS2 -VASc, adjusted odds ratio (AOR), 4.39 [95% CI, 3.99-4.83]), low risk of bleeding (ORBIT, AOR, 1.87 [95% CI, 1.72-2.03]), not having a recorded history of dementia (AOR, 1.81 [95% CI, 1.65-1.98]) and male sex (AOR, 1.29 [95% CI, 1.22-1.35]) were independently associated with OAC initiation. Direct-acting oral anticoagulant (DOAC) use increased from 11.9% in 2011 to 94.0% of all OAC initiations in April 2019 (P < .001). CONCLUSIONS: The proportion of newly diagnosed patients with AF initiated on OAC increased markedly following the introduction of the DOACs. Of those initiated, 9 in 10 were receiving a DOAC at the end of the study period. There is potential underuse in women and individuals with dementia.

Comparison of renin-angiotensin-aldosterone system inhibitors with other antihypertensives in association with coronavirus disease-19 clinical outcomes.

BACKGROUND: Reports on the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting. We performed this meta-analysis to find conclusive evidence. METHODS: We searched published articles through PubMed, EMBASE and medRxiv from 5 January 2020 to 3 August 2020. Studies that reported clinical outcomes of patients with COVID-19, stratified by the class of antihypertensives, were included. Random and fixed-effects models were used to estimate pooled odds ratio (OR). RESULTS: A total 36 studies involving 30,795 patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR = 0.79, 95% CI: [0.67, 0.95]) compared with those receiving non-RAAS inhibitor antihypertensives. However, further sub-meta-analysis showed that specific RAAS inhibitors did not show a reduction of poor COVID-19 outcomes when compared with any class of antihypertensive except beta-blockers (BBs). For example, compared to calcium channel blockers (CCBs), neither angiotensin-I-converting enzyme inhibitors (ACEIs) (OR = 0.91, 95% CI: [0.67, 1.23]) nor angiotensin-II receptor blockers (ARBs) (OR = 0.90, 95% CI: [0.62, 1.33]) showed a reduction of poor COVID-19 outcomes. When compared with BBs, however, both ACEIs (OR = 0.85, 95% CI: [0.73, 0.99) and ARBs (OR = 0.72, 95% CI: [0.55, 0.94]) showed an apparent decrease in poor COVID-19 outcomes. CONCLUSIONS: RAAS inhibitors did not increase the risk of mortality or severity of COVID-19. Differences in COVID-19 clinical outcomes between different class of antihypertensive drugs were likely due to the underlying comorbidities for which the antihypertensive drugs were prescribed, although adverse effects of drugs such as BBs could not be excluded.

Outcomes of Medication Misadventure Among People With Cognitive Impairment or Dementia: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate mortality and hospitalization outcomes associated with medication misadventure (including medication errors [MEs], such as the use of potentially inappropriate medications [PIMs], and adverse drug events [ADEs]) among people with cognitive impairment or dementia. DATA SOURCES: Ovid MEDLINE, Ovid EMBASE, Ovid International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials were searched from inception to December 2019. STUDY SELECTION AND DATA EXTRACTION: Relevant studies using any study design were included. Reviewers independently performed critical appraisal and extracted relevant data. DATA SYNTHESIS: The systematic review included 10 studies that reported the outcomes of mortality or hospitalization associated with medication misadventure, including PIMs (n=5), ADEs (n=2), a combination of MEs and ADEs (n=2), and drug interactions (n=1). Five studies examining the association between PIMs and mortality/hospitalization were included in the meta-analyses. Exposure to PIMs was not associated with either mortality (odds ratio [OR]=1.36; 95%CI=0.79-2.35) or hospitalization (OR=1.02; 95%CI=0.83-1.26). In contrast, single studies indicated that ADEs with cholinesterase inhibitors were associated with mortality and hospitalization. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Individuals with cognitive impairment or dementia are at increased risk of medication misadventure; based on relatively limited published data, this does not necessarily translate to increased mortality and hospitalization. CONCLUSIONS: Overall, medication misadventure was not associated with mortality or hospitalization in people with cognitive impairment or dementia, noting the limited number of studies, difficulty in controlling potential confounding variables, and that most studies focus on PIMs.

Clinical impact of antipsychotic and benzodiazepine reduction: findings from a multicomponent psychotropic reduction program within long-term aged care.

OBJECTIVES: To explore the relationships between dose changes to antipsychotic and/or benzodiazepine medications and resident outcomes, including variations in neuropsychiatric symptoms, quality of life (QoL), and social withdrawal, within a multicomponent, interdisciplinary antipsychotic and benzodiazepine dose reduction program. DESIGN: Prospective, observational, longitudinal study. INTERVENTION: The Reducing Use of Sedatives (RedUSe) project involved 150 Australian Long-Term Care Facilities (LTCFs) incorporating auditing and benchmarking of prescribing, education, and multidisciplinary sedative reviews. SETTING: A convenience sample of LTCFs (n = 28) involved in RedUSe between January 2015 and March 2016. PARTICIPANTS: Permanent residents (n = 206) of LTCFs involved in RedUSe taking an antipsychotic and/or benzodiazepine daily. Residents were excluded if they had a severe psychiatric condition where antipsychotic therapy should generally be maintained long-term (e.g., bipolar disorder, schizophrenia) or were considered end-stage palliative. MEASUREMENTS: Neuropsychiatric symptoms (Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory (CMAI)), QoL (Assessment of Quality of Life-4D), and social withdrawal (Multidimensional Observation Scale for Elderly Subjects-withdrawal subscale) were measured at baseline and 4 months where nursing staff completed psychometric tests as proxy raters. RESULTS: There was no evidence that psychometric measures were worsened following dose reductions. In fact, dose reduction was associated with small, albeit non-statistically significant, improvements in behavior, particularly less physically non-aggressive behavior with both drug groups (-0.36 points per 10% reduction in antipsychotic dose, -0.17 per 10% reduction in benzodiazepine dose) and verbally agitated behavior with benzodiazepine reduction (-0.16 per 10% dose reduction), as measured with the CMAI. Furthermore, antipsychotic reduction was associated with non-statistically significant improvements in QoL and social withdrawal. CONCLUSIONS: Antipsychotic and benzodiazepine dose reduction in LTCFs was not associated with deterioration in neuropsychiatric symptoms, QoL, or social withdrawal. Trends toward improved agitation with antipsychotic and benzodiazepine dose reduction require further evaluation in larger, prospective, controlled studies.

Ten-year trends in prescribing of antiarrhythmic drugs in Australian primary care patients with atrial fibrillation.

Despite changes in antiarrhythmic drug (AAD) choice in patients with atrial fibrillation (AF), trends in AAD prescribing remain not investigated. We aimed to examine these changes using a nationwide Australian general practice data from 2009 to 2018. Over the 10 years, AAD prescribing in patients with AF decreased, which was mainly due to a reduction in the use of amiodarone, sotalol and digoxin. In contrast, the use of beta-blockers and flecainide increased.

Drug compliance and the Morisky Adherence Scale: An expression of concern and a warning.

WHAT IS KNOWN AND OBJECTIVE: Every prescriber knows that patients often do not take their medicines as prescribed. Hippocrates, the wise man of Kos, knew over two millennia ago. Our objective is to comment on the types of studies aimed at understanding and optimizing drug usage and to draw attention to the need to seek approval before using or citing the Morisky adherence scale. COMMENT: The study of prescribing and how patients use their medicines is important. As part of this effort, the results of investigations of how patients adhere to drug prescriptions can be informative. However, the results are meaningful only if the methods used for doing the measurements are valid and made explicit. We were surprised when a team of our authors were threatened with legal action for citing the Morisky Adherence Scale and explaining how some authors had obtained their adherence scores. Adherence studies are but one facet of the study of prescribing aimed at improving clinical outcomes. Other aspects include investigating the quality of prescribing, and how unnecessary medicines can be deprescribed to improve the quality of care and reduce the risk of adverse effects. WHAT IS NEW AND CONCLUSION: The study of optimal prescribing is an important endeavour and adherence studies are but one aspect. We report that using and citing the Morisky Adherence scale in any detail is a risky business. Prior approval is required unless one is prepared to pay up, retrospectively. We require all authors to certify they have no conflicts of interest with respect to the scale.

Pharmacological management of post-traumatic stress disorder and its associated nightmares: A survey of psychiatrists.

WHAT IS KNOWN AND OBJECTIVE: To describe the pharmacological management of post-traumatic stress disorder (PTSD) by psychiatrists, with a focus on their use of clinical guidelines and the role of prazosin for nightmares. METHODS: An online survey of Australian and New Zealand psychiatrists was conducted. Aspects included respondent demographics, familiarity and usage of guidelines for PTSD, and opinions on the safety and efficacy of prazosin for PTSD-associated nightmares. RESULTS AND DISCUSSION: A total of 157 responses were recorded, 106 of which were complete. The most frequently used guideline for PTSD management was over 10 years old and used by only 48% of respondents. Peer-reviewed scientific journals were the most common additional source used by psychiatrists to inform their practice. For the targeted treatment of nightmares, 35 different medications had been trialled by respondents. Prazosin had been prescribed by 86% of psychiatrists for PTSD-associated nightmares, with only 2% reporting it to be ineffective in reducing nightmare frequency and/or intensity. Psychiatrists who were familiar with prazosin-mentioning guidelines (P < .05) and those who more frequently treat patients with PTSD (P < .01) were most likely to have prescribed prazosin. WHAT IS NEW AND CONCLUSION: Psychiatrists generally do not rely on guidelines to inform the treatment of PTSD. Off-label prescription of prazosin for PTSD-associated nightmares occurs frequently, with positive perceived outcomes, despite conflicting published evidence and a lack of local guideline recommendations for its use.

Emerging concepts and directed therapeutics for the management of asthma: regulating the regulators.

Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted.

Drug-associated non-pyrogenic hyperthermia: a narrative review.

PURPOSE: Hyperthermia occurs when heat accumulation surpasses the body's ability for heat dissipation. Many drugs may affect thermoregulation. This narrative review aimed to provide an overview of the current literature concerning reports of drug-associated non-pyrogenic hyperthermia. METHODS: A comprehensive search was performed across 5 databases covering the period of inception to March 2019, for publications that reported hyperthermia associated with drug use. Studies that reported potential drug association with hyperthermia due to altered thermoregulatory mechanisms were included. Case reports of less than 3 cases were excluded, as well as hyperthermia due to other causes, such as hypersensitivity, malignant hyperthermia and neuroleptic malignant syndrome. The primary outcomes of interest were hospitalisation and mortality. RESULTS: The literature search initially identified a total of 2609 records. Based on full-text analysis, 11 articles met the inclusion criteria, of which there were 5 case-control studies, 2 case series and 4 retrospective analyses. Studies reported heat-related hospitalisations or emergency department presentations associated with the use of psychotropics (antipsychotics, antidepressants and anxiolytics), anticholinergics, antihistamines, diuretics, cardiovascular agents, non-steroidal anti-inflammatory drugs and anticoagulants. Psychotropic drugs were reported to be associated with increased heat-related mortality, other than through neuroleptic malignant syndrome, but findings varied among the studies. CONCLUSION: Given the relative lack of publications, more research is necessary to study specific effects of drugs on body temperature and the likelihood of inducing non-pyrogenic hyperthermia. In particular, psychotropics, anticholinergics, diuretics and cardiovascular agents are of interest for future studies.

Association between anticholinergic drug burden and mortality in older people: a systematic review.

PURPOSE: The purpose of the study is to conduct a systematic review of studies examining the association between anticholinergic burden and mortality in older individuals. METHODS: A literature search was performed to identify relevant studies, using MEDLINE, EMBASE, PsycINFO and CENTRAL, from January 1990 to December 2018. We included studies of patients with a mean age of 65 years or older where the anticholinergic burden was estimated using anticholinergic risk assessment tools, and associations between anticholinergic load and mortality were investigated. The primary outcome of interest was the association between anticholinergic burden and mortality. RESULTS: Twenty-seven studies were included. These were three cross-sectional, one nested case-control and 23 prospective or retrospective cohort studies. Most studies were determined to be of good quality. A total of 15 studies reported a positive correlation between anticholinergic burden and mortality, while the remaining 10 studies did not report a significant association. Eighteen out of 27 studies (80%) had a short follow-up period of 1 year or less. Among the five high-quality studies that met all the domains of the quality assessment criteria, four showed a positive association. CONCLUSION: The variation in results could relate to the quality of the studies, follow-up period, anticholinergic risk assessment tool used and the study setting. Sixty-three percent (n = 17) of all the included studies, but almost all of the high-quality studies with an extended follow-up, reported a positive correlation between anticholinergic burden and mortality. Further high-quality research, using standardized measures and with adequate follow-up periods, is required to confirm the relationship between anticholinergic burden and mortality.

Quality use of medicines in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) affects drug elimination and patients with CKD require appropriate adjustment of renally cleared medications to ensure safe and effective pharmacotherapy. The main objective of this study was to determine the extent of potentially inappropriate prescribing (PIP; defined as the use of a contraindicated medication or inappropriately high dose according to the kidney function) of renally-cleared medications commonly prescribed in Australian primary care, based on two measures of kidney function. A secondary aim was to assess agreement between the two measures. METHODS: Retrospective analysis of routinely collected de-identified Australian general practice patient data (NPS MedicineWise MedicineInsight from January 1, 2013, to June 1, 2016; collected from 329 general practices). All adults (aged ≥18 years) with CKD presenting to general practices across Australia were included in the analysis. Patients were considered to have CKD if they had two or more estimated glomerular filtration rate (eGFR) recorded values < 60 mL/min/1.73m2, and/or two urinary albumin/creatinine ratios ≥3.5 mg/mmol in females (≥2.5 mg/mmol in males) at least 90 days apart. PIP was assessed for 49 commonly prescribed medications using the Cockcroft-Gault (CG) equation/eGFR as per the instructions in the Australian Medicines Handbook. RESULTS: A total of 48,731 patients met the Kidney Health Australia (KHA) definition for CKD and had prescriptions recorded within 90 days of measuring serum creatinine (SCr)/estimated glomerular filtration rate (eGFR). Overall, 28,729 patients were prescribed one or more of the 49 medications of interest. Approximately 35% (n = 9926) of these patients had at least one PIP based on either the Cockcroft-Gault (CG) equation or eGFR (CKD-EPI; CKD-Epidemiology Collaboration Equation). There was good agreement between CG and eGFR while determining the appropriateness of medications, with approximately 97% of the medications classified as appropriate by eGFR also being considered appropriate by the CG equation. CONCLUSION: This study highlights that PIP commonly occurs in primary care patients with CKD and the need for further research to understand why and how this can be minimised. The findings also show that the eGFR provides clinicians a potential alternative to the CG formula when estimating kidney function to guide drug appropriateness and dosing.

Drug-associated hyperthermia: A longitudinal analysis of hospital presentations.

WHAT IS KNOWN AND OBJECTIVE: Hyperthermia occurs when heat accumulation surpasses the body's ability for heat dissipation. Many drugs can affect thermoregulation through mechanisms including altering the neurotransmitters that cause increased heat production or decreased heat loss and may, therefore, be associated with hyperthermia. This study aimed to examine hospitalizations and emergency department (ED) presentations due to hyperthermia and to investigate the potential association with drug therapy. METHODS: A retrospective analysis of ED presentations and hospitalizations due to hyperthermia in all four major hospitals in Tasmania, Australia, between July 2010 and December 2018 was performed. Data of patients aged ≥18 years were extracted from the hospital digital medical records and analysed for the prevalence, trends and various potential risk factors for hyperthermia, such as age, environmental temperature and drug therapy. RESULTS: This study included 224 patients. The data illustrated a trend with time, albeit not statistically significant, towards increasing hospital presentations due to hyperthermia. Antiepileptics (P = .03) and furosemide (P = .04) were the most frequently used drugs in patients with primary hyperthermia. The high use of levothyroxine in the study population (6.7%) stood out compared with the estimated national average (2.1%). Various drug classes associated with hyperthermia were used significantly more in the age group ≥60 years, suggesting polypharmacy in the elderly as a contributing factor for hyperthermia. WHAT IS NEW AND CONCLUSION: This study reports a possible association of some drugs, particularly diuretics (furosemide), antiepileptics and levothyroxine, with hyperthermia. Healthcare professionals should be aware of the increasing prevalence of hyperthermia and the possible involvement of drugs.

Antifungal Drug Use for Onychomycosis.

BACKGROUND: Onychomycoses are fungal nail infections affecting predominantly toenails, and mainly caused by dermatophyte fungi, molds and some Candida species. Nail infections can be mild with purely cosmetic implications, but they can also negatively influence quality of life. The deep-seated nature of fungi within the nail plate, prolonged treatment, poor patient adherence, frequent recurrences, and development of resistance to various antimicrobial agents make onychomycosis difficult to successfully treat. AREAS OF UNCERTAINTY: When and how should clinicians prescribe systemic and topical antifungal drugs for onychomycosis? DATA SOURCES: A narrative review was undertaken of the current literature identified in Medline, Scopus, CINAHL, the Cochrane library, and Google Scholar. RESULTS: Treatment is often lengthy and requires persistence and patient education. Definitive mycological diagnosis, and an individualized evaluation of risks and benefits of different treatments are imperative before initiating therapy. The choice of treatment can be influenced by the age and general health of the patient, the causative organism, the number of affected nails, and the extent of nail involvement. Oral antifungals offer greater likelihood of a cure than topicals, but oral therapy carries greater risks and requires closer monitoring. Oral terbinafine is the treatment of choice, followed by itraconazole pulse regimen. The newly approved topical agents, efinaconazole and tavaborole, were superior to placebo in clinical trials and appear to produce slightly improved mycological cure rates compared to previous topicals, but further direct comparisons are needed. CONCLUSIONS: The treatment of onychomycosis can be challenging, as most therapeutic options are lengthy, expensive and potentially unsuccessful.