Transdermal Rotigotine at End-of-Life for Parkinson's Disease: Association With Measures of Distress.

BACKGROUND: End-of-life (EOL) care for Parkinson's disease (PD) can be challenging when oral medications are no longer tolerated. MEASURES: To assess EOL prescribing for people with PD (PWP), focusing on rotigotine dosing and proxy measures of distress: benzodiazepine and opioid use. INTERVENTION: A retrospective audit of patient records from PWP who died between January 2019 and May 2022 at the Royal Hobart Hospital (RHH), Australia, was conducted. Data was systematically collated on demographics, symptoms, levodopa equivalent daily dose (LEDD) and rotigotine, oral morphine equivalent (OME) and benzodiazepine doses in the last 72 hours of life . OUTCOMES: Pain (72%), respiratory secretions (66%) and agitation (66%) were the most documented EOL symptoms. 83% (n = 52) of PWP were eligible for rotigotine and, of those, 13% (n = 7) received the correct dose, 38% (n = 20) a lower dose, 12% (n = 6) a higher dose and 37% (n = 19) did not receive any. Rotigotine dose was positively associated with total (P = 0.016) and PRN (P = 0.037) benzodiazepine dose. LEDD was positively associated with total benzodiazepine (P = 0.018) and total OME dose (P = 0.046). Contraindicated dopamine antagonists were prescribed for 43% of PWP and administered in 31% of those cases. CONCLUSIONS: Rotigotine dose and admission LEDD were both associated with proxy measures of distress in the last 72 hours of life. This suggests cautious use of rotigotine at EOL. LEDD may help identify patients at risk of distress. Rates of inappropriate prescribing and symptom prevalence were high, indicating a need for further staff education to optimize the care of PWP.

Syndrome of inappropriate antidiuretic hormone secretion after functional endoscopic sinus surgery.

Functional endoscopic sinus surgery (FESS) is effective in cases of sinusitis where pharmacological treatment has not been successful. Patients undergoing FESS have reported an 85% improvement in symptoms as measured by the quality of life scores. Despite its convincing therapeutic benefit, complications sometimes occur with potentially dire consequences. We report the case of a 69-year-old patient who underwent FESS for recurrent frontal sinusitis and developed a syndrome of inappropriate antidiuretic hormone secretion (SIADH) on Day 3 post-operatively. To our knowledge, this is the first documented case of SIADH arising after an endoscopic intervention for frontal sinusitis.

Genetic conjugation of components in two pneumococcal fusion protein vaccines enhances paediatric mucosal immune responses.

Streptococcus pneumoniae colonises the upper respiratory tract and can cause pneumonia, meningitis and otitis media. Existing pneumococcal conjugate vaccines are expensive to produce and only protect against 13 of the 90+ pneumococcal serotypes; hence there is an urgent need for the development of new vaccines. We have shown previously in mice that pneumolysin (Ply) and a non-toxic variant (Δ6Ply) enhance antibody responses when genetically fused to pneumococcal surface adhesin A (PsaA), a potentially valuable effect for future vaccines. We investigated this adjuvanticity in human paediatric mucosal primary immune cell cultures. Adenoidal mononuclear cells (AMNC) from children aged 0-15 years (n=46) were stimulated with conjugated, admixed or individual proteins, cell viability and CD4+ T-cell proliferative responses were assessed using flow cytometry and cytokine secretion was measured using multiplex technology. Proliferation of CD4+ T-cells in response to PsaAPly, was significantly higher than responses to individual or admixed proteins (p=0.002). In contrast, an enhanced response to PsaAΔ6Ply compared to individual or admixed proteins only occurred at higher concentrations (p<0.01). Evaluation of cytotoxicity suggested that responses occurred when Ply-induced cytolysis was inhibited, either by fusion or mutation, but importantly an additional toxicity independent immune enhancing effect was also apparent as a result of fusion. Responses were MHC class II dependent and had a Th1/Th17 profile. Genetic fusion of Δ6Ply to PsaA significantly modulates and enhances pro-inflammatory CD4+ T-cell responses without the cytolytic effects of some other pneumolysoids. Membrane binding activity of such proteins may confer valuable adjuvant properties as fusion may assist Δ6Ply to deliver PsaA to the APC surface effectively, contributing to the initiation of anti-pneumococcal CD4+ T-cell immunity.

Grommets (ventilation tubes) for recurrent acute otitis media in children.

BACKGROUND: Acute suppurative otitis media is one of the most common infectious diseases in childhood. Recurrent acute otitis media is defined for the purposes of this review as either three or more acute infections of the middle ear cleft in a six-month period, or at least four episodes in a year. Strategies for managing the condition include the assessment and modification of risk factors where possible, repeated courses of antibiotics for each new infection, antibiotic prophylaxis and the insertion of ventilation tubes (grommets). OBJECTIVES: To establish whether ventilation tube insertion reduces the frequency of episodes of recurrent acute otitis media and the proportion of children with symptoms of ear disease. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2008), MEDLINE (1950 to 2008), EMBASE (1974 to 2008), CINAHL, mRCT (the metaRegister of Controlled Trials for ongoing/unpublished trials), NRR (National Research Register), LILACs, KoreaMed, IndMed, PakMediNet, Zetoc, ISI Proceedings and Cambridge Scientific Abstracts. Reference lists of articles retrieved from the electronic searches were scanned for further trials. Systematic reviews and other meta-analyses were also searched for and their reference lists scanned. Contact was sought with authors of published trials and other experts in the field. The date of the last search was March 2008. SELECTION CRITERIA: No trials that included a treatment and a control group that met the inclusion criteria were excluded. Abstracts were screened and full text articles of studies that met our inclusion criteria obtained. Two authors independently applied the inclusion criteria. Studies included in the review underwent quality assessment performed independently by all authors adapting the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the authors and synthesised descriptively. Five randomised controlled trials were identified, of which two fulfilled the inclusion criteria. MAIN RESULTS: Two studies involving 148 children were included in the review. One of these studies, involving 95 children, showed that ventilation tube insertion leads to a mean reduction of 1.5 episodes of acute otitis media in the first six months after treatment. This study also showed a significant increase in the proportion of children with no episodes of AOM (p < 0.001) in the ventilation tube group. The other included study also found a higher proportion of patients in the ventilation tube group had no episodes of AOM in the six months after intervention, but the difference did not reach statistical significance (p = 0.16). AUTHORS' CONCLUSIONS: Ventilation tubes have a significant role in maintaining a 'disease-free' state in the first six months after insertion. Further research is required to investigate the effect beyond six months. Clinicians should consider the possible adverse effects of grommet insertion before surgery is undertaken.

The effect of the total intravenous anesthesia compared with inhalational anesthesia on the surgical field during endoscopic sinus surgery.

BACKGROUND: Bleeding during endoscopic sinus surgery (ESS) may increase complications and negatively effect the surgery and its outcome. The aim of this study was to compare the surgical field in patients in whom total intravenous anesthesia (TIVA) is used as opposed to inhalation anesthesia. A prospective randomized controlled trial was performed. METHODS: Fifty-six patients undergoing ESS were randomly assigned to receive either inhaled sevoflurane with incremental doses of fentanyl (n = 28) or TIVA via a propofol and remifentanil infusion (n = 28) for their general anesthesia. The surgical field was graded every 15 minutes using a validated scoring system. RESULTS: The two groups were matched for surgical procedure and computed tomography scores. Patients in the TIVA group were found to have a significantly lower surgical grade score than in the sevoflurane group (p < 0.001). Surgical grade score increased with time in both groups. Mean arterial pressure and pulse were found to influence the surgical field independently (p = 0.003 and p = 0.036 respectively). Mean surgical field grade scores were higher in the patients with allergic fungal sinusitis and nasal polyposis as opposed to chronic rhinosinusitis without polyps or fungus. Lund-Mackay computed tomography scores were found to correlate positively with surgical grade (Spearman rank correlation, p = 0.001). CONCLUSION: In patients undergoing ESS, TIVA results in a better surgical field than inhalational anesthesia.

Endoscopic sinus surgery rescue of failed osteoplastic flap with fat obliteration.

PURPOSE OF REVIEW: The modified endoscopic Lothrop procedure has been used as an alternative to osteoplastic flap with obliteration in the management of chronic frontal sinusitis. More recently it has been used to rescue cases of failed osteoplastic flap. This article reviews the recent literature regarding endoscopic rescue of failed osteoplastic flap with obliteration. RECENT FINDINGS: Endoscopic sinus surgery is indicated in cases of osteoplastic flap failure when there is objective evidence of mucocele formation. All patients require CT and MR imaging preoperatively. Clinical improvement can be achieved in up to 89% of patients in the first 12 to 18 months postoperatively. SUMMARY: The modified endoscopic Lothrop procedure is effective in the management of failed osteoplastic flap with obliteration in the short term. Long-term evaluation of this technique is still required. Endoscopic rescue is technically challenging and requires an experienced surgeon, ideally with access to image guidance equipment.

GATA3 and NeuroD distinguish auditory and vestibular neurons during development of the mammalian inner ear.

The function of the zinc finger transcription factor GATA3 was studied in a newly established, conditionally immortal cell line derived to represent auditory sensory neuroblasts migrating from the mouse otic vesicle at embryonic day E10.5. The cell line, US/VOT-33, expressed GATA3, the bHLH transcription factor NeuroD and the POU-domain transcription factor Brn3a, as do auditory neuroblasts in vivo. When GATA3 was knocked down reversibly with antisense oligonucleotides, NeuroD was reversibly down-regulated. Auditory and vestibular neurons form from neuroblasts that express NeuroD and that migrate from the antero-ventral, otic epithelium at E9.5-10.5. On the medial side, neuroblasts and epithelial cells express GATA3 but on the lateral side they do not. At E13.5 most auditory neurons express GATA3 but no longer express NeuroD, whereas vestibular neurons express NeuroD but not GATA3. Neuroblasts expressing NeuroD and GATA3 were located in the ventral, otic epithelium, the adjacent mesenchyme and the developing auditory ganglion. The results suggest that auditory and vestibular neurons arise from different, otic epithelial domains and that they gain their identity prior to migration. In auditory neuroblasts, NeuroD appears to be dependent on the expression of GATA3.