Wilfred W Yeo

Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older

BACKGROUND A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229 .).

Chronic treatment with simvastatin upregulates muscarinic M1/4 receptor binding in the rat brain

Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [(3)H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [(3)H]pirenzepine binding, predominantly in the prefrontal cortex (171%, P<0.001), primary motor cortex (153%, P=0.001), cingulate cortex (109%, P<0.001), hippocampus (138%, P<0.001), caudate putamen (122%, P=0.002) and nucleus accumbens (170%, P<0.001) compared with controls; while lower but still significant increases of [(3)H]pirenzepine binding were observed in the examined regions following simvastatin (10 mg/kg/day) treatment. Our results also provide strong evidence that chronic simvastatin administration, especially at a low dosage, up-regulates M1/4 receptor binding, which is likely to be independent of its muscarinic agonist-like effect. Alterations in [(3)H]pirenzepine binding in the examined brain areas may represent the specific regions that mediate the clinical effects of simvastatin treatment on cognition and memory via the muscarinic cholinergic system. These findings contribute to a better understanding of the critical roles of simvastatin in treating neurodegenerative disorders, via muscarinic receptors.

The burden of healthcare-associated Clostridium difficile infection in a non-metropolitan setting

OBJECTIVE Healthcare-associated Clostridium difficile infection (HCA-CDI) remains a major cause of morbidity and mortality in industrialized countries. However, few data exist on the burden of HCA-CDI in multi-site non-metropolitan settings. This study examined the introduction of an antimicrobial stewardship programme (ASP) in relation to HCA-CDI rates, and the effect of HCA-CDI on length of stay (LOS) and hospital costs. METHODS A comparative before-and-after intervention study of patients aged ≥16 years with HCA-CDI from December 2010 to April 2016 across the nine hospitals of a non-metropolitan health district in New South Wales, Australia was undertaken. The intervention comprised a multi-site ASP supported by a clinical decision support system, with subsequent introduction of email feedback of HCA-CDI cases to admitting medical officers. MAIN OUTCOME MEASURES HCA-CDI rates, comparative LOS and hospital costs, prior use of antimicrobials and proton pump inhibitors, and appropriateness of CDI treatment. RESULTS HCA-CDI rates rose from 3.07 to 4.60 cases per 10,000 occupied bed-days pre-intervention, and remained stable at 4 cases per 10,000 occupied bed-days post-intervention (P=0.24). Median LOS (17 vs six days; P<0.01) and hospital costs (AU

Sedation and Analgesia in Unconscious Palliative Care Patients: Can Bispectral Index monitoring add to our understanding?

19,222 vs

Use of romiplostim in patients with chronic idiopathic thrombocytopenic purpura during perioperative period

7861; P<0.01) were significantly greater for HCA-CDI cases (N=91) than for matched controls (N=172). Half of the patients with severe HCA-CDI (4/8) did not receive initial appropriate treatment (oral vancomycin). CONCLUSIONS HCA-CDI placed a significant burden on the regional and rural health service through increased LOS and hospital costs. Interventions targeting HCA-CDI could be employed to consolidate the effects of ASPs.

Impact of an antimicrobial stewardship interventio n onappropriateness of prescribing for community-acquiredpneumonia in an Australian regional hospital

Most palliative care patients enter a phase of unconsciousness prior to death. The transition is usually gradual. It results from the weight of disease progression and, to a varying degree, the sedative effect of prescribed medication. In a small number of patients, reduced consciousness is a direct consequence of palliative sedation, introduced with the informed consent of the patient to relieve intractable suffering from symptoms that do not respond to standard treatment measures (1-3). The justification for palliative sedation is based on the understanding that rendering such patients unconscious with proportionate doses of a sedative and an analgesic is the only remaining therapeutic option as death approaches. The provision of good palliative care is more challenging once patients are unresponsive and unable to make their needs known. Assessments and decisions about treatment rely on subjective measures, which may or may not include observational scales. While the goal of these practices is to ensure patient comfort and dignity, the value and interrater reliability of observations and scales that monitor symptoms and depth of sedation have not been adequately tested (4, 5). Recent studies suggest that unresponsiveness — which commonly accompanies unconsciousness — does not automatically imply unawareness, and measures that rely on a person’s ability to react to stimulation may be misleading and could contribute to an uncomfortable death that goes unrecognized (6-8). Further research utilizing more objective methods, such as Bispectral Index (BIS) monitoring, may not only help to establish the reliability of subjective assessments but may also determine the efficacy of treatments currently provided to patients at the end of life (4, 5).

Impact of an antimicrobial stewardship intervention on appropriateness of prescribing for community-acquired pneumonia in an Australian regional hospital

In patients with chronic idiopathic thrombocytopenic purpura (cITP), the platelet count tends to be quite variable and, in the majority of cases, specific therapy is not warranted on a regular basis. However, patients with low platelet count (<30 nL) or with bleeding complications would require therapy, such as prednisolone, intravenous immunoglobulin infusions, splenectomy and/or immunosuppression. Romiplostim, a thrombopoietin agonist, has also proven to be useful in improving platelet counts. cITP can be associated with bleeding complications perioperatively. As such, a higher platelet count is warranted (approximately 80 nL), particularly for invasive surgeries, such as orthopaedic surgery, cardio‐thoracic surgery, head and neck surgery and abdominal surgery, where risk of bleeding is quite high already.

Spontaneous pneumomediastinum: a rare entity but not to be missed: Letters to the Editor

Community‐acquired pneumonia (CAP) is the second commonest indication for antibiotic use in Australian hospitals and is therefore a frequent target for antimicrobial stewardship. A single‐centre prospective study was conducted in a regional referral hospital comparing management of adult patients with CAP before and after an educational intervention. We demonstrated a reduction in duration of therapy and reduced inappropriate use of ceftriaxone‐based regimens for non‐severe CAP.

Pilot study on causes of delirium in orthogeriatrics

Community‐acquired pneumonia (CAP) is the second commonest indication for antibiotic use in Australian hospitals and is therefore a frequent target for antimicrobial stewardship. A single‐centre prospective study was conducted in a regional referral hospital comparing management of adult patients with CAP before and after an educational intervention. We demonstrated a reduction in duration of therapy and reduced inappropriate use of ceftriaxone‐based regimens for non‐severe CAP.

Managing advanced dementia, advance care planning for dementia patients

restrictions of OTC medications that were available. Since these changes, there has not been a single case reported in Britain. Less restrictive changes were made within Australia over this time period and ibuprofen– codeine still remains available for purchase through non-prescription pathways. A meta-analysis by Frei et al. published in the Medical Journal of Australia in 2010 reported a 27 case series of misuse of OTC ibuprofen–codeine analgesics. Over half a million Australians use ‘pain killers’ for non-medical purposes and OTC preparations are the third most common form of substance abuse in Australia. Nurofen Plus has the highest content of codeine available in an OTC preparation and 26 of the 27 cases used supratherapeutic doses of Nurofen Plus with 2 cases of hypokalaemia, 4 intensive care unit admissions and 1 patient requiring dialysis. Ibuprofen–codeine combinations remain accessible in non-prescription preparations and are a legal source of obtaining opioid medication. This case documents the potentially life-threatening adverse reactions that can occur with inappropriate use of ibuprofen–codeine in combination. It demonstrates the need for tighter restrictions to be enforced to limit public access. Medical practitioners should be made aware of the potential effects and should specifically question patients about the use of OTC drugs. The serious harmful effects need to be conveyed to the public.