Sam Kosari

Centrally Administered Resistin Enhances Sympathetic Nerve Activity to the Hindlimb but Attenuates the Activity to Brown Adipose Tissue

Resistin, an adipokine, is believed to act in the brain to influence energy homeostasis. Plasma resistin levels are elevated in obesity and are associated with metabolic and cardiovascular disease. Increased muscle sympathetic nerve activity (SNA) is a characteristic of obesity, a risk factor for diabetes and cardiovascular disease. We hypothesized that resistin affects SNA, which contributes to metabolic and cardiovascular dysfunction. Here we investigated the effects of centrally administered resistin on SNA to muscle (lumbar) and brown adipose tissue (BAT), outputs that influence cardiovascular and energy homeostasis. Overnight-fasted rats were anesthetized, and resistin (7 μg) was administered into the lateral cerebral ventricle (intracerebroventricular). The lumbar sympathetic nerve trunk or sympathetic nerves supplying BAT were dissected free, and nerve activity was recorded. Arterial blood pressure, heart rate, body core temperature, and BAT temperature were also recorded. Responses to resistin or vehicle were monitored for 4 h after intracerebroventricular administration. Acutely administered resistin increased lumbar SNA but decreased BAT SNA. Mean arterial pressure and heart rate, however, were not significantly affected by resistin. BAT temperature was significantly reduced by resistin, and there was a concomitant fall in body temperature. The findings indicate that resistin has differential effects on SNA to tissues involved in metabolic and cardiovascular regulation. The decreased BAT SNA and the increased lumbar SNA elicited by resistin suggest that it may contribute to the increased muscle SNA and reduced energy expenditure observed in obesity and diabetes.

Central resistin enhances renal sympathetic nerve activity via phosphatidylinositol 3-kinase but reduces the activity to brown adipose tissue via extracellular signal-regulated kinase 1/2.

Resistin is an adipokine, originally identified in adipose tissue, and its plasma levels are elevated in obesity. Characteristics of obesity include impaired metabolic regulation and cardiovascular dysfunction, such as increased sympathetic nerve activity (SNA) to the kidney and skeletal muscle vasculature. Resistin can affect energy homeostasis through central mechanisms that include reduced food intake and reduced thermogenesis, and can also increase lumbar SNA via a central action. The present study investigated: (i) the effect of centrally‐administered resistin on SNA targeting the kidney and (ii) the intracellular signalling pathways mediating the changes in SNA innervating the kidney and brown adipose tissue (BAT) induced by resistin. Intracerebroventricular resistin (7 μg) injected into overnight fasted, anaesthetised rats induced a significant increase in renal SNA by approximately 40%. This response was prevented when phosphatidylinositol 3‐kinase (PI3K) was inhibited by i.c.v. administration of LY294002 (5 μg). Resistin reduced BAT SNA and this response was delayed by 150 min when extracellular‐regulated kinase (ERK)1/2 was inhibited by i.c.v. administration of U0126. The findings indicate that resistin increases renal SNA via PI3K and reduces BAT SNA via ERK1/2.

We have had a gutful: The need for deprescribing proton pump inhibitors

Proton pump inhibitor (PPI) prescribing may often be inappropriate and expose patients to a risk of adverse effects, while incurring unnecessary healthcare expenditure. Our objective was to determine PPI usage in Australia since 2002 and review international studies investigating inappropriate PPI prescribing, including those that discussed interventions to address this issue.

Feasibility of integrating residential care pharmacists into aged care homes to improve quality use of medicines: Study protocol for a non-randomised controlled pilot trial

Older adults are particularly susceptible to iatrogenic disease and communicable diseases, such as influenza. Prescribing in the residential aged care population is complex, and requires ongoing review to prevent medication misadventure. Pharmacist-led medication review is effective in reducing medication-related problems; however, current funding arrangements specifically exclude pharmacists from routinely participating in resident care. Integrating an on-site clinical pharmacist into residential care teams is an unexplored opportunity to improve quality use of medicines in this setting. The primary objective of this pilot study is to investigate the feasibility of integrating a residential care pharmacist into the existing care team. Secondary outcomes include incidence of pharmacist-led medication review, and incidence of potential medication problems based on validated prescribing measures. This is a cross-sectional, non-randomised controlled trial with a residential care pharmacist trialled at a single facility, and a parallel control site receiving usual care and services only. The results of this hypothesis-generating pilot study will be used to identify clinical outcomes and direct future larger scale investigations into the implementation of the novel residential care pharmacist model to optimise quality use of medicines in a population at high risk of medication misadventure.

Stakeholder perspectives about general practice pharmacists in the Australian Capital Territory: a qualitative pilot study

Previous studies have found that integrating non-dispensing pharmacists in general practice may improve patient safety, improve patient outcomes, deliver health system efficiencies and generate savings. However, the employment of pharmacists in general practice is not common in Australia. A naturalistic study was conducted in the Australian Capital Territory with three general practices, each employing a part-time pharmacist for 12 months. This study reports on stakeholder perspectives of the benefits, barriers and enablers for integrating pharmacists into general practice. Patients, practice staff and community pharmacists that had interacted with a practice pharmacist were asked to complete a self-administered questionnaire. Patient questionnaire respondents (n=44) reported that a practice pharmacist was beneficial and wanted to see this continue. Practice pharmacists were also perceived beneficial by primary healthcare employees surveyed (n=42). Opinions were further explored by individual semi-structured interviews (n=20). The qualitative data explored five themes: perception of the practice pharmacist, collaboration with doctors, pharmacist roles, sustainability and community pharmacy aspects. Patients welcomed improved understanding about their medication, whereas general practice staff appreciated pharmaceutical advice about patients with chronic conditions. Participants discussed options to fund practice pharmacists longer term, which was identified as the main barrier to widespread roll out.

Sleep Disturbances and Nightmares in a Patient Treated with Prazosin.

Prazosin is increasingly being used off-label to treat nightmares in patients with posttraumatic stress disorder. The literature about the psychiatric adverse effects of prazosin is very limited. We present a case in which low-dose prazosin was associated with nightmares and sleep disturbances in an elderly patient without previously diagnosed mental illness or coexisting environmental risk factors for nightmares. Insomnia and hallucinations are listed as some of the rare side effects of prazosin by the manufacturer. Prazosin could be associated with rare psychiatric adverse effects and sleep disturbances. Particular attention is required in identifying these adverse effects, which can be difficult to distinguish from other drug-related side effects in the elderly particularly because they are often using multiple medications.

The Role of Pharmacists in General Practice in Asthma Management: A Pilot Study

Background: Asthma is principally managed in general practice. Appropriate prescribing and medication use are essential, so general practice pharmacists appear suitable to conduct asthma management consultations. This pilot study aimed to evaluate the asthma management role of a pharmacist in general practice. Methods: Analysis of an activity diary and stakeholder interviews were conducted to identify interventions in asthma management; determine whether asthma control changed following pharmacist input; and determine acceptability of asthma management review by a pharmacist in one general practice in Canberra, Australia. Results: Over 13 months, the pharmacist saw 136 individual patients. The most common activities were asthma control assessment; recommendations to adjust medication or device; counselling on correct device use; asthma action plan development and trigger avoidance. For patients with multiple consultations, the mean Asthma Control Test score improved from the initial to last visit (14.4 ± 5.2 vs. 19.3 ± 4.7, n = 23, p < 0.0001). Eight of the 19 (42%) patients moved from having poor to well-controlled asthma. Case studies and qualitative data indicated probable hospital admission avoidance and stakeholder acceptability of asthma management by a practice pharmacist. Conclusions: This pilot study demonstrated it is feasible, acceptable and potentially beneficial to have a general practice pharmacist involved in asthma management. Fuller evaluation is warranted.

Chemotherapy in Pancreatic Cancer: A Systematic Review

Background and Aim: Pancreatic cancer is one of the most fatal cancers. Cytotoxic chemotherapy remains the mainstream treatment for unresectable pancreatic cancer. This systematic review evaluated and compared the overall survival (OS) and progression-free survival (PFS) outcomes obtained from recent phase 2 and 3 clinical trials of pancreatic cancer chemotherapy. Materials and methods: Thirty-two studies were included and compared based on chemotherapy agents or combinations used. Additionally, outcomes of first-line versus second-line chemotherapy in pancreatic cancer were compared. Results: In studies that investigated the treatments in adjuvant settings, the highest OS reported was for S-1 in patients, who received prior surgical resection (46.5 months). In neoadjuvant settings, the combination of gemcitabine, docetaxel, and capecitabine prior to the surgical resection had promising outcomes (OS of 32.5 months). In non-adjuvant settings, the highest OS reported was for the combination of temsirolimus plus bevacizumab (34.0 months). Amongst studies that investigated second-line treatment, the highest OS reported was for the combination of gemcitabine plus cisplatin (35.5 months), then temsirolimus plus bevacizumab (34.0 months). Conclusions: There is a need to develop further strategies besides chemotherapy to improve the outcomes in pancreatic cancer treatment. Future studies should consider surgical interventions, combination chemotherapy, and individualized second-line treatment based on the prior chemotherapy.

Practice pharmacists and the opportunity to support general practitioners in deprescribing in the older person

Problems associated with the use of medicines in society continue to be a significant public health burden, with the brunt being borne by older people.1–3 The higher risk of medicine-related adverse events and hospitalisations in older adults is caused primarily by age-related pharmacokinetic and pharmacodynamic changes, and a higher number of chronic conditions and resultant polypharmacy, which is often associated with the use of potentially inappropriate medicines.3–5 Adverse drug events (ADEs) frequently involve predictable high-risk situations, such as multiple drug use in the elderly, which are amenable to prevention through better systems and ways of working by health professionals.

Challenges and Opportunities in the Management of Onychomycosis

Onychomycosis is an increasingly common fungal nail infection, chiefly caused by dermatophyte fungi. The disease is notoriously difficult to treat due to the deep-seated nature of fungi within the nail plate, prolonged treatment requirements, poor patient adherence and frequent recurrences. Given the poor efficacy of currently available topical and systemic therapies, there is a renewed interest in exploring alternative treatment modalities for onychomycosis. Natural therapies, physical treatments and various combination therapies have all shown potential for the management of onychomycosis, though research on many of these methods is still in preliminary stages. Further large, well-designed, randomised controlled trials are necessary to confirm the efficacy of these novel treatments in order to make formal recommendations regarding their use in the management of onychomycosis.