No abstract available.
Sinusitis*

INTRODUCTIONMultidrug-resistant (MDR) Gram-negative healthcare-associated infections are prevalent in Singaporean hospitals. An accurate assessment of the socioeconomic impact of these infections is necessary in order to facilitate appropriate resource allocation, and to judge the costeffectiveness of targeted interventions.

MATERIALS AND METHODSA retrospective cohort study involving inpatients with healthcare-associated Gram-negative bacteraemia at 2 large Singaporean hospitals was conducted to determine the hospitalisation costs attributed to multidrug resistance, and to elucidate factors affecting the financial impact of these infections. Data were obtained from hospital administrative, clinical and financial records, and analysed using a multivariate linear regression model.

RESULTSThere were 525 survivors of healthcare-associated Gram-negative bacteraemia in the study cohort, with 224 MDR cases. MDR bacteraemia, concomitant skin and soft tissue infection, higher APACHE II score, ICU stay, and appropriate definitive antibiotic therapy were independently associated with higher total hospitalisation costs, whereas higher Charlson comorbidity index and concomitant urinary tract infection were associated with lower costs. The excess hospitalisation costs attributed to MDR infection was $8638.58. In the study cohort, on average, 62.3% of the excess cost attributed to MDR infection was paid for by government subvention.

CONCLUSIONMultidrug resistance in healthcare-associated Gram-negative bacteraemia is associated with higher financial costs--a significant proportion of which are subsidised by public funding in the form of governmental subvention. More active interventions aimed at controlling antimicrobial resistance are warranted, and the results of our study also provide possible benchmarks against which the cost-effectiveness of such interventions can be assessed.

Aged ; Anti-Bacterial Agents ; economics ; therapeutic use ; Bacteremia ; drug therapy ; economics ; Cohort Studies ; Cost of Illness ; Cross Infection ; drug therapy ; economics ; Drug Resistance, Multiple, Bacterial ; Female ; Gram-Negative Bacterial Infections ; drug therapy ; economics ; Hospitalization ; economics ; Humans ; Intensive Care Units ; economics ; Linear Models ; Male ; Middle Aged ; Prevalence ; Retrospective Studies ; Severity of Illness Index ; Singapore

The habenula (Hb) is small but important brain structure, anatomically and functionally links the forebrain with the midbrain to modulate various neuropsychiatric functions associated with drug addiction and emotion-associated dysfunctions. Several reports suggested that the dysfunction of Hb-related functions affected the Hb structurally and functionally. However, the technical limitation has awaited the solid conclusion of whether Hb change due to depression is likely to occur in certain subnuclei of the Hb. To probe this possibility, we developed 3-dimensional reconstruction methods for the high-resolution volumetric analysis of Hb and the mRNA levels at the given volume in normal or lipopolysaccharide (LPS)-mediated mouse model of depression. Notably, we discovered that the volume reduction was prominent in medial Hb but not in lateral Hb after LPS treatments. On the other hand, the RNA expression levels of known Hb regional markers such as Tac1 (dorsal part of medial Hb), ChAT (ventral part of medial Hb), and Tacr1 (medial and lateral Hb) were all decreased in all Hb subnuclei in LPS-injected mice. Accordingly, accurate volumetry with marker labeling was not feasible. Collectively, these established 3D analyses of mouse Hb successfully and precisely determine the volume-based changes of small brain structure, which should be applicable in a wider range of mouse models or pathological specimens.
Animals ; Brain ; Depression ; Gene Expression ; Habenula ; Hand ; Mesencephalon ; Mice ; Prosencephalon ; RNA ; RNA, Messenger ; Substance-Related Disorders

The retinal activity for vision requires a precise synaptic connectivity. Shank proteins at postsynaptic sites of excitatory synapses play roles in signal transmission into the postsynaptic neuron. However, the correlation of Shank 2 expression with neuronal differentiation in the developing retina remains to be elucidated regardless of previous evidences of Shank 2 expression in retina. Herein, we demonstrated that with progression of development, Shank 2 is initially detected in the inner plexiform layer at P2, and then intensively detected in inner plexiform layer, outer plexiform layer, and ganglion cell layer at P14, which was closely colocalized to the neurofilament expression. Shank 2 was, however, not colocalized with glial fibrillary acidic protein. Shank 2 expression was increased in the differentiated retinoblastoma cells, which was mediated by ERK 1/2 activation. Moreover, Shank 2 expression was colocalized with neurofilament at the dendritic region of cells. In conclusion, our data suggests that Shank 2 is expressed in the neurons of the developing retina and could play a critical role in the neuronal differentiation of the developing retina.
Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Animals ; Astrocytes/cytology/metabolism ; Cell Differentiation/*physiology ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases/metabolism ; *Gene Expression Regulation, Developmental ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics/*metabolism ; Neurofilament Proteins/metabolism ; Neurons/cytology/*physiology ; *Retina/cytology/growth & development/physiology ; Retinoblastoma/metabolism/pathology

Background: and Purpose Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD). Methods: This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. Results: The difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study– Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (f0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. Conclusions IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.