Prevalence, characteristics and risk factors of frequently readmitted patients to an internal medicine service.

BACKGROUND: Unplanned hospital readmissions (HRA), which have been used as key performance index of healthcare quality, are becoming more prevalent. They are associated with substantial financial burden to hospital systems and considerable impacts on patients' physical and mental health. Patients with frequent readmissions are not well studied. AIMS: To determine the prevalence, characteristics and risk factors associated with frequent readmissions (FRA) to an internal medicine service at a tertiary public hospital. METHOD: A retrospective observational study was conducted at an internal medicine service in a tertiary teaching hospital between 1 January 2010 and 30 June 2016. FRA was defined as four or more readmissions within 12 months of discharge from the index admission (IA). Demographic and clinical characteristics and potential risk factors were evaluated. RESULTS: A total of 50 515 patients was included; 1657 (3.3%) had FRA and were associated with nearly 2.5 times higher in 12-month mortality rates. They were older, had higher rates of indigenous Australians (3.2%), more disadvantaged status (index of relative socio-economic disadvantage decile of 5.3) and more comorbidities (mean Charlson comorbidity index 1.4) in comparison, to infrequent readmission group. The mean length of hospital stay during the IA was 6 days for FRA group (21.4% staying more than 7 days) with higher incidence of discharge against medical advice (2.0% higher). Intensive care unit admission rate was 6.6% for FRA group compared with 3.9% for infrequent readmission group. Multivariate analysis showed mental disease and disorders, neoplastic, alcohol/drug use and alcohol/drug-induced organic mental disorders are associated with FRA. CONCLUSION: The risk factors associated with FRA were older age, indigenous status, being socially disadvantaged, having higher comorbidities and discharging against medical advice. Conditions that lead to FRA were mental disorders, alcohol/drug use and alcohol/drug-induced organic mental disorders and neoplastic disorders.

The Brain is Not Flat: Conformal Electrode Arrays Diminish Complications of Subdural Electrode Implantation, A Series of 117 Cases.

BACKGROUND: Intracranial recordings are integral to evaluating patients with pharmacoresistant epilepsy whom noninvasive testing fails to localize seizure focus. Although stereo-electroencephalography is the preferred method of intracranial recordings in most centers, subdural electrode (SDE) implantation is necessary in selected cases. OBJECTIVE: To identify imaging correlates that predict SDE complications (extra-axial fluid collections [EFCs]), and determine if modifications that diminish stiffness of electrode sheets reduce complications. METHODS: A prospective epilepsy surgery database was used to identify adults undergoing craniotomy for SDE implantation over a 14-year period. EFCs and midline shift were measured via magnetic resonance imaging and computed tomography imaging. Correlation analyses and multivariable logistic regression explored associations between use of conformal arrays, serial order of patients, previous ipsilateral intracranial surgery, midline shift, number of SDEs, and neurologic complications. RESULTS: A total of 111 consecutive patients (59 female) underwent 117 craniotomies (mean, 115 electrode contacts) for SDE implantation. There were 8 surgical complications, 3 in the first 17 (17.7%). and 5 (after electrode modifications) in a subsequent 100 craniotomies (5.0%). We noted an increase in electrode numbers implanted over time (P < 0.001) and decreased midline shift with conformal grids (ρ = - 0.32; P < 0.001). A multivariable regression showed that midline shift correlated with complications (odds ratio, 2.32; 95% confidence interval, 1.12-4.78; P = 0.023). CONCLUSIONS: Hemorrhagic complications after SDE implantation are difficult to detect because of artifact from electrodes, but predictable by prominent midline shift (>4 mm). Risks inherent to SDE implantation may be minimized using conformal grids. With symptomatic EFCs, a single electrode cable exit site allows hematoma evacuation without terminating intracranial recordings.

Gaussian Mixture Models for Probabilistic Classification of Breast Cancer.

In the era of omics-driven research, it remains a common dilemma to stratify individual patients based on the molecular characteristics of their tumors. To improve molecular stratification of patients with breast cancer, we developed the Gaussian mixture model (GMM)-based classifier. This probabilistic classifier was built on mRNA expression data from more than 300 clinical samples of breast cancer and healthy tissue and was validated on datasets of ESR1, PGR, and ERBB2, which encode standard clinical markers and therapeutic targets. To demonstrate how a GMM approach could be exploited for multiclass classification using data from a candidate marker, we analyzed the insulin-like growth factor I receptor (IGF1R), a promising target, but a marker of uncertain importance in breast cancer. The GMM defined subclasses with downregulated (40%), unchanged (39%), upregulated (19%), and overexpressed (2%) IGF1R levels; inter- and intrapatient analyses of IGF1R transcript and protein levels supported these predictions. Overexpressed IGF1R was observed in a small percentage of tumors. Samples with unchanged and upregulated IGF1R were differentiated tumors, and downregulation of IGF1R correlated with poorly differentiated, high-risk hormone receptor-negative and HER2-positive tumors. A similar correlation was found in the independent cohort of carcinoma in situ, suggesting that loss or low expression of IGF1R is a marker of aggressiveness in subsets of preinvasive and invasive breast cancer. These results demonstrate the importance of probabilistic modeling that delves deeper into molecular data and aims to improve diagnostic classification, prognostic assessment, and treatment selection. SIGNIFICANCE: A GMM classifier demonstrates potential use for clinical validation of markers and determination of target populations, particularly when availability of specimens for marker development is low.

Analysis of Morbidity and Outcomes Associated With Use of Subdural Grids vs Stereoelectroencephalography in Patients With Intractable Epilepsy.

Importance: A major change has occurred in the evaluation of epilepsy with the availability of robotic stereoelectroencephalography (SEEG) for seizure localization. However, the comparative morbidity and outcomes of this minimally invasive procedure relative to traditional subdural electrode (SDE) implantation are unknown. Objective: To perform a comparative analysis of the relative efficacy, procedural morbidity, and epilepsy outcomes consequent to SEEG and SDE in similar patient populations and performed by a single surgeon at 1 center. Design, Setting and Participants: Overall, 239 patients with medically intractable epilepsy underwent 260 consecutive intracranial electroencephalographic procedures to localize their epilepsy. Procedures were performed from November 1, 2004, through June 30, 2017, and data were analyzed in June 2017 and August 2018. Interventions: Implantation of SDE using standard techniques vs SEEG using a stereotactic robot, followed by resection or laser ablation of the seizure focus. Main Outcomes and Measures: Length of surgical procedure, surgical complications, opiate use, and seizure outcomes using the Engel Epilepsy Surgery Outcome Scale. Results: Of the 260 cases included in the study (54.6% female; mean [SD] age at evaluation, 30.3 [13.1] years), the SEEG (n = 121) and SDE (n = 139) groups were similar in age (mean [SD], 30.1 [12.2] vs 30.6 [13.8] years), sex (47.1% vs 43.9% male), numbers of failed anticonvulsants (mean [SD], 5.7 [2.5] vs 5.6 [2.5]), and duration of epilepsy (mean [SD], 16.4 [12.0] vs17.2 [12.1] years). A much greater proportion of SDE vs SEEG cases were lesional (99 [71.2%] vs 53 [43.8%]; P < .001). Seven symptomatic hemorrhagic sequelae (1 with permanent neurological deficit) and 3 infections occurred in the SDE cohort with no clinically relevant complications in the SEEG cohort, a marked difference in complication rates (P = .003). A greater proportion of SDE cases resulted in resection or ablation compared with SEEG cases (127 [91.4%] vs 90 [74.4%]; P < .001). Favorable epilepsy outcomes (Engel class I [free of disabling seizures] or II [rare disabling seizures]) were observed in 57 of 75 SEEG cases (76.0%) and 59 of 108 SDE cases (54.6%; P = .003) amongst patients undergoing resection or ablation, at 1 year. An analysis of only nonlesional cases revealed good outcomes in 27 of 39 cases (69.2%) vs 9 of 26 cases (34.6%) at 12 months in SEEG and SDE cohorts, respectively (P = .006). When considering all patients undergoing evaluation, not just those undergoing definitive procedures, favorable outcomes (Engel class I or II) for SEEG compared with SDE were similar (57 of 121 [47.1%] vs 59 of 139 [42.4%] at 1 year; P = .45). Conclusions and Relevance: This direct comparison of large matched cohorts undergoing SEEG and SDE implantation reveals distinctly better procedural morbidity favoring SEEG. These modalities intrinsically evaluate somewhat different populations, with SEEG being more versatile and applicable to a range of scenarios, including nonlesional and bilateral cases, than SDE. The significantly favorable adverse effect profile of SEEG should factor into decision making when patients with pharmacoresistant epilepsy are considered for intracranial evaluations.

Demonstration of ion channel synthesis by isolated squid giant axon provides functional evidence for localized axonal membrane protein translation.

Local translation of membrane proteins in neuronal subcellular domains like soma, dendrites and axon termini is well-documented. In this study, we isolated the electrical signaling unit of an axon by dissecting giant axons from mature squids (Dosidicus gigas). Axoplasm extracted from these axons was found to contain ribosomal RNAs, ~8000 messenger RNA species, many encoding the translation machinery, membrane proteins, translocon and signal recognition particle (SRP) subunits, endomembrane-associated proteins, and unprecedented proportions of SRP RNA (~68% identical to human homolog). While these components support endoplasmic reticulum-dependent protein synthesis, functional assessment of a newly synthesized membrane protein in axolemma of an isolated axon is technically challenging. Ion channels are ideal proteins for this purpose because their functional dynamics can be directly evaluated by applying voltage clamp across the axon membrane. We delivered in vitro transcribed RNA encoding native or Drosophila voltage-activated Shaker KV channel into excised squid giant axons. We found that total K+ currents increased in both cases; with added inactivation kinetics on those axons injected with RNA encoding the Shaker channel. These results provide unambiguous evidence that isolated axons can exhibit de novo synthesis, assembly and membrane incorporation of fully functional oligomeric membrane proteins.

Bipolar disorder and related mood states are not associated with endothelial function of small arteries in adults without heart disease.

BACKGROUND: Individuals with bipolar disorder are at increased risk for adverse cardiovascular disease (CVD) events. This study aimed to assess endothelial function and wave reflection, a risk factor for CVD, as measured by finger plethysmography in bipolar disorder to investigate whether CVD risk was higher in bipolar disorder and altered during acute mood episodes. We hypothesized that EndoPAT would detect a lower reactive hyperemia index (RHI) and higher augmentation index (AIX) in individuals with bipolar disorder compared with controls. Second, we predicted lower RHI and higher AIX during acute mood episodes. METHODS: Reactive hyperemia index and augmentation index, measures of microvascular endothelial function and arterial pressure wave reflection respectively, were assessed using the EndoPAT 2000 device in a sample of 56 participants with a DSM-IV diagnosis of bipolar I disorder with 82 measures spanning different mood states (mania, depression, euthymia) and cross-sectionally in 26 healthy controls. RESULTS: RHI and AIX were not different between adults with and without bipolar disorder (mean age 40.3 vs. 41.2years; RHI: 2.04±0.67 vs. 2.05±0.51; AIX@75 (AIX adjusted for heart rate of 75): 1.4±19.7 vs. 0.8±22.4). When modeled in linear mixed models with a random intercept (to account for repeated observations of persons with bipolar disorder) and adjusting for age and sex, there were no significant differences between those with bipolar disorder and controls (p=0.89 for RHI; p=0.85 for AIX@75). CONCLUSIONS: Microvascular endothelial function and wave reflection estimated by finger plethysmography were unable to detect differences between adults with and without bipolar disorder or changes with mood states. Future research is necessary to identify more proximal and sensitive, yet relevant, biomarkers of abnormal mood-related influences on CVD risk or must target higher risk samples.

A novel flagellar sheath protein, FcpA, determines filament coiling, translational motility and virulence for the Leptospira spirochete.

Leptospira are unique among bacteria based on their helical cell morphology with hook-shaped ends and the presence of periplasmic flagella (PF) with pronounced spontaneous supercoiling. The factors that provoke such supercoiling, as well as the role that PF coiling plays in generating the characteristic hook-end cell morphology and motility, have not been elucidated. We have now identified an abundant protein from the pathogen L. interrogans, exposed on the PF surface, and named it Flagellar-coiling protein A (FcpA). The gene encoding FcpA is highly conserved among Leptospira and was not found in other bacteria. fcpA(-) mutants, obtained from clinical isolates or by allelic exchange, had relatively straight, smaller-diameter PF, and were not able to produce translational motility. These mutants lost their ability to cause disease in the standard hamster model of leptospirosis. Complementation of fcpA restored the wild-type morphology, motility and virulence phenotypes. In summary, we identified a novel Leptospira 36-kDa protein, the main component of the spirochete's PF sheath, and a key determinant of the flagella's coiled structure. FcpA is essential for bacterial translational motility and to enable the spirochete to penetrate the host, traverse tissue barriers, disseminate to cause systemic infection and reach target organs.

Cost-effectiveness of culture-guided antimicrobial prophylaxis for the prevention of infections after prostate biopsy.

BACKGROUND: Clinical findings suggest that the use of rectal culture-guided antibiotic prophylaxis reduces the infection rate following transrectal ultrasound-guided prostate biopsy (TRUSBx). METHODS: A decision-analytic model was designed to compare the outcomes of TRUSBx performed with (rectal culture-guided group) and without (standard ciprofloxacin prophylaxis) rectal swab culture-guided antimicrobial prophylaxis in Hong Kong. The post-biopsy infection rate, infection-related costs, quality-adjusted life years (QALYs) lost for infection, and incremental cost per QALY saved (ICER) were assessed. Model inputs were retrieved from local epidemiology data and the medical literature. A sensitivity analysis was performed to test the robustness of the model results. RESULTS: Base-case analysis showed that the infection rate in the culture-guided group was reduced from 2.42% to 0.23% and saved 0.0002 QALYs, with a lower cost (USD 31.4 versus USD 55.6) (USD 1=HKD 7.8). The number needed to screen to prevent an infection episode was 45.7. The hospital days avoided per 100 patients using culture-guided prophylaxis was 7.08 days. The relative effectiveness of culture-guided antimicrobial prophylaxis versus standard prophylaxis in carriers and non-carriers of FQ-resistant rectal flora were identified as potential influencing factors. In 10000 Monte Carlo simulations, ICERs of the culture-guided group were below the willingness-to-pay threshold 99.12% of the time. CONCLUSIONS: Using rectal culture-guided antimicrobial prophylaxis for men undergoing TRUSBx appears to be a cost-saving strategy to avert post-biopsy infection and QALY loss in Hong Kong.

Genome, Proteome and Structure of a T7-Like Bacteriophage of the Kiwifruit Canker Phytopathogen Pseudomonas syringae pv. actinidiae.

Pseudomonas syringae pv. actinidiae is an economically significant pathogen responsible for severe bacterial canker of kiwifruit (Actinidia sp.). Bacteriophages infecting this phytopathogen have potential as biocontrol agents as part of an integrated approach to the management of bacterial canker, and for use as molecular tools to study this bacterium. A variety of bacteriophages were previously isolated that infect P. syringae pv. actinidiae, and their basic properties were characterized to provide a framework for formulation of these phages as biocontrol agents. Here, we have examined in more detail φPsa17, a phage with the capacity to infect a broad range of P. syringae pv. actinidiae strains and the only member of the Podoviridae in this collection. Particle morphology was visualized using cryo-electron microscopy, the genome was sequenced, and its structural proteins were analysed using shotgun proteomics. These studies demonstrated that φPsa17 has a 40,525 bp genome, is a member of the T7likevirus genus and is closely related to the pseudomonad phages φPSA2 and gh-1. Eleven structural proteins (one scaffolding) were detected by proteomics and φPsa17 has a capsid of approximately 60 nm in diameter. No genes indicative of a lysogenic lifecycle were identified, suggesting the phage is obligately lytic. These features indicate that φPsa17 may be suitable for formulation as a biocontrol agent of P. syringae pv. actinidiae.

A single-domain FlgJ contributes to flagellar hook and filament formation in the Lyme disease spirochete Borrelia burgdorferi.

FlgJ plays a very important role in flagellar assembly. In the enteric bacteria, flgJ null mutants fail to produce the flagellar rods, hooks, and filaments but still assemble the integral membrane-supramembrane (MS) rings. These mutants are nonmotile. The FlgJ proteins consist of two functional domains. The N-terminal rod-capping domain acts as a scaffold for rod assembly, and the C-terminal domain acts as a peptidoglycan (PG) hydrolase (PGase), which allows the elongating flagellar rod to penetrate through the PG layer. However, the FlgJ homologs in several bacterial phyla (including spirochetes) often lack the PGase domain. The function of these single-domain FlgJ proteins remains elusive. Herein, a single-domain FlgJ homolog (FlgJ(Bb)) was studied in the Lyme disease spirochete Borrelia burgdorferi. Cryo-electron tomography analysis revealed that the flgJ(Bb) mutant still assembled intact flagellar basal bodies but had fewer and disoriented flagellar hooks and filaments. Consistently, Western blots showed that the levels of flagellar hook (FlgE) and filament (FlaB) proteins were substantially decreased in the flgJ(Bb) mutant. Further studies disclosed that the decreases of FlgE and FlaB in the mutant occurred at the posttranscriptional level. Microscopic observation and swarm plate assay showed that the motility of the flgJ(Bb) mutant was partially deficient. The altered phenotypes were completely restored when the mutant was complemented. Collectively, these results indicate that FlgJ(Bb) is involved in the assembly of the flagellar hook and filament but not the flagellar rod in B. burgdorferi. The observed phenotype is different from that of flgJ mutants in the enteric bacteria.