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Falls are a significant, but often preventable problem among elders. To identify possible risk factors for falls, this study examined differences between frail elders reporting falls and those reporting no falls in the past year. From a sample of 831 frail elders, defined as older persons with activity of daily living (ADL) limitations, 347 (42%) reported one or more falls. Subjects reporting one or more falls in the past year had more motor, functional, psychological, and cognitive impairment than non-fallers. In-home assessment and intervention help prevent falls in frail elders. [ABSTRACT FROM AUTHOR]

Background: Unpreserved single-dose unit (SDU) eye drops are commonly used to avoid benzalkonium chloride-related toxicity. Although intended for single use, many patients report off-label repeated use of SDUs over a prolonged period. We investigated whether repeated use of dexamethasone 0.1% SDUs in the same patient increases the bacterial contamination rate., Methods: We prospectively enrolled patients scheduled for inpatient corneal and glaucoma surgery receiving dexamethasone 0.1% SDU four times per day from the same vial. To assess contamination rates, one drop from the vial was cultured immediately after opening the SDU (t0), 10 hours later after four drop applications (t10) and 24 hours after opening without further drop applications (t24). Conjunctival swabs were taken before and after drop application. Contamination rate was assessed with a standard clinical culturing protocol without introducing a positive control., Results: 110 eyes of 109 patients were evaluated. Drops collected immediately after opening the SDU (t0) were contaminated in 9/110 cultures (8.1%). At t10, 13/110 cultures were contaminated (11.8%; p=0.267) and 11/110 at t24 (10.0%; t24 vs t0; p=1.00). In 5 of 21 cases of contaminated drops at t10 and/or t24, the same isolates were cultured from the initial conjunctival swab and the SDU. In three cases, the same bacterial species was found in consecutive samples., Conclusion: The contamination rate of the SDU did not increase after multiple use within 24 hours. Contamination from fingertip flora was more likely than from ocular surface flora. Reuse of dexamethasone 0.1% SDU in the same patient within 24 hours appears to be safe., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare results from facility-level and state-level severe maternal morbidity (SMM) reviews in Illinois., Design: We report descriptive characteristics about SMM cases and compare the results of both review processes, including the primary cause, assessment of preventability, and factors that contributed to the severity of the SMM cases., Setting: All birthing hospitals in Illinois., Participants: A total of 81 SMM cases were reviewed by a facility-level committee and the state-level review committee. SMM was defined as any intensive care or critical care unit admission and/or transfusion of 4 or more units of packed red blood cells from conception to 42 days postpartum., Results: Among the cases reviewed by both committees, hemorrhage was the primary cause of morbidity, with 26 (32.1%) and 38 (46.9%) hemorrhage cases identified by the facility-level and state-level committees, respectively. Both committees identified infection/sepsis (n = 12) and preeclampsia/eclampsia (n = 12) as the next most common causes of SMM. State-level review found more cases potentially preventable (n = 29, 35.8% vs n = 18, 22.2%) and more cases not preventable but improvement in care needed (n = 31, 38.3% vs n = 27, 33.3%). State-level review found more provider and system opportunities to alter the SMM outcome and fewer patient opportunities than facility-level review., Conclusion: State-level review found more SMM cases potentially preventable and identified more opportunities to improve care than facility-level review. State-level review has the potential to strengthen facility-level reviews by identifying opportunities to improve the review process and develop recommendations and tools to aid facility-level reviews., Competing Interests: The authors have indicated that they have no potential conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The number of patients with chronic diseases and subsequent visits to various healthcare professionals has been rising over the past decades, exposing patients to potential risks of receiving conflicting medication information. This study aims to investigate the prevalence of conflicting information on medications perceived by chronic patients in Switzerland and to understand its impact on patients' medication self-management and navigation in the healthcare system., Participants: This cross-sectional study included adult patients taking at least one prescribed medication for at least 6 months, who had visited at least two physicians in the past 3 months., Main Outcome Measures: Data on patients' perceptions of conflicting information were collected in person through a 17-item questionnaire available on paper and electronically with four domains: (1) whether the patient had perceived any conflicting information, (2) categories of conflicting information, (3) impact and (4) sources involved in the conflicting information., Results: Of the 405 included patients, 47% perceived conflicting information related to one or more medication topics including indication, schedule, dosage, risk, severity or duration of side effects. Patients who perceived conflicting information were prescribed more drugs than those perceiving no conflicting information (p<0.01). Consequently, 65% of the participants modified their navigation of the healthcare system and 34% reported medication non-adherence. General practitioners (82%), specialist physicians (74%) and pharmacists (49%) were the healthcare professionals most often involved in conflicting information. Experience with the medication, its package insert and significant others were more frequently involved in conflicting information than internet or social media., Conclusion: Nearly half the patients in our study perceived conflicting information in the outpatient healthcare system, which can decrease medication effectiveness and pose safety issues. This issue is widely overlooked and unaddressed. Consistency of information among healthcare providers in partnership with patients should be reinforced through guidelines and new models of interprofessional care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A 34-year-old gravida 2, para 1 woman at 37+4 weeks of pregnancy presented with abdominal pain. She had no medical history. Complete examination was unremarkable. After hours of monitoring, the patient abruptly deteriorated. An emergency cesarean delivery revealed a ruptured uterus with significant issues. Cautious monitoring is essential for such patients with atypical pain., (© 2022 The Authors.)

Background: The cesarean delivery rate has been rising in recent years, having associated maternal morbidities. Elective induction of labor has also been seen to rise during this same time period., Objective: This current study investigated the difference in the cesarean delivery rate between induction of labor and spontaneous labor among nulliparous, term, singleton, and vertex-presenting women., Study Design: A retrospective cohort in a single institution over a seven-year period was used for this analysis, observing the difference in cesarean delivery rate at different term gestational ages and neonatal morbidity using the 5-minute Apgar score < 5., Results: A statistically significant difference was found in cesarean delivery rate between those women whose labor was induced and those whose labor began spontaneously, at each term gestational age of labor initiation (P < 0.001). The proportion of indications for induction was described (i.e. elective vs. medically-indicated), and no difference was found for neonatal morbidity between the groups analyzed, using the 5-minute Apgar score as the perinatal outcome measure., Conclusion: A comparison was made between spontaneous and induced labor regarding the resultant cesarean delivery rate, and a significant difference was found favoring spontaneous labor. This should be considered when electing to deliver using an induction methodology for nulliparous women, especially when there are no medical indications for it., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: This study tested a theory-based adherence-enhancing intervention: the "Interprofessional Medication Adherence Program" (IMAP) to increase human immunodeficiency virus (HIV) retention in care., Methods: We retrospectively compared our intervention center (intervention group [IG]) with a standard of care center (control group [CG]) both participating in the Swiss HIV Cohort Study between 2004 and 2012. Endpoints were defined as >6-month and >12-month gaps in care for intervals of care longer than 6 and 12 months without any blood draw. Inverse probability of treatment weights was used to adjust for differences between patients at the 2 centers. Viral failure was defined as ribonucleic acid ≥50 copies/mL after 24+ weeks on antiretrovirals., Results: The IG included 451 patients, CG 311. In the IG, 179 (40%) patients took part in the IMAP for a median of 27 months (interquartile range, 12-45). Gaps in care of ≥6 months were significantly more likely to happen in the CG versus IG (74.6% vs 57%, P < .001). The median time until the first treatment gap was longer in the IG vs CG (120 vs 84 weeks, P < .001). Gaps in care of ≥12 months evaluated in 709 (93%) patients were significantly more likely to occur in the CG compared with the IG (22.6% vs 12.5%, P < .001). The rate of viral failure was significantly lower in the IG (8.3% vs 15.1%, P = .003)., Conclusions: This study, in a real-world setting, shows the effectiveness of the IMAP to reduce 6- and 12-month gaps in follow up among people with HIV. These results should be confirmed by studies in other settings., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To investigate the diagnostic accuracy of optical coherence tomography angiography (OCTA) in detecting vascular characteristics of chorio-retinal disease., Methods: Evidence acquisition: We searched Web of Science, Scopus, and Medline by the citation of references and complemented these electronic searches by checking the list of references of included and review articles. Screening, selection, assessment, and extraction was performed in parallel by two authors., Results: Evidence synthesis: Systematic review and exploratory meta-analysis. The ten studies that contributed to the meta-analysis enrolled 440 eyes and allowed constructing ten two-by-two tables. The tables reported on detection of choroidal neovascularization (CNV) in eyes suffering from either age-related macular degeneration (4), central serous chorioretinopathy (2), myopia (2), foveomacular vitelliform dystrophy (1), or a mixed cohort suffering from multiple retinal diseases (1). Of the ten studies, six used a cohort and four a case-control design. We found a pooled sensitivity of 0.90 (95% confidence intervals (CIs): 0.82-0.95) and a pooled specificity of 0.97 (95% CI: 0.89-0.99). Corresponding positive and negative likelihood ratios were 32.3 (95% CI: 7.4-141.6) and 0.10 (95% CI: 0.06-0.20), respectively. No pooling was possible for retinal vascular parameters of diabetic retinopathy, polypoidal choroidal vasculopathy, or detection of CNV activity., Conclusions: The results of highly biased and heterogeneous studies assessing the diagnostic performance of OCTA highlight the need for further analyses of methodologically sound and sufficiently sized clinical evaluations.

This report provides examples of using 3-dimensional ultrasound diagnostically in gynecology. The cost efficiency it provides and the wide range of applications it has support the routine use of this ultrasound technology in the practice of gynecology., (© 2018 by the American Institute of Ultrasound in Medicine.)

Introduction: Prognostication of cardiac arrest patients admitted to the intensive care unit (ICU) may influence treatment decision, but remains challenging. We evaluated the incremental usefulness of routine blood markers from different biological pathways for predicting fatal outcome and neurological deficits in cardiac arrest patients., Methods: We prospectively included consecutive, adult cardiac arrest patients upon ICU admission. We recorded initial clinical parameters and measured blood markers of cardiac injury/stress (troponin, BNP, CK), inflammation/infection (WBC, CRP, procalcitonin) and shock (lactate, creatinine, urea). The primary and secondary endpoints were all-cause in-hospital mortality and bad neurological outcome defined by the Cerebral Performance Category (CPC) score., Results: Mortality in the 321 included patients was 49% (n = 156). Procalcitonin (adjusted odds ratio 1.84, 95%CI 1.34 to 2.53, p < 0.001; AUC 0.73) and lactate (adjusted odds ratio 7.29, 95%CI 3.05 to 17.42, p < 0.001; AUC 0.70) were identified as independent prognostic factors for mortality and significantly improved discrimination of a parsimonious clinical model including resuscitation measures (no-flow time, shockable rhythm) and initial vital signs (Glasgow coma scale, respiratory rate) from an AUC of 0.79 to 0.84 (p < 0.001). Cardiac markers did not further improve the model. Results for neurological outcome were similar with model improvements by procalcitonin and lactate from AUC 0.83 to 0.87 (p = 0.004)., Conclusion: Assessment of routine markers of inflammation/infection and shock provide significant improvements for prognostication of cardiac arrest patients, while cardiac markers did not further improve statistical models. Combination of blood markers and clinical parameters may help to improve initial management decisions in this vulnerable patient population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Vesicular stomatitis virus (VSV) expressing the Ebola virus (EBOV) glycoprotein (GP) in place of the VSV glycoprotein G (VSV/EBOV-GP) is a promising EBOV vaccine candidate which has already entered clinical phase 3 studies. Although this chimeric virus was tolerated overall by volunteers, it still caused viremia and adverse effects such as fever and arthritis, suggesting that it might not be sufficiently attenuated. In this study, the VSV/EBOV-GP vector was further modified in order to achieve attenuation while maintaining immunogenicity. All recombinant VSV constructs were propagated on VSV G protein expressing helper cells and used to immunize guinea pigs via the intramuscular route. The humoral immune response was analysed by EBOV-GP-specific fluorescence-linked immunosorbent assay, plaque reduction neutralization test and in vitro virus-spreading inhibition test that employed recombinant VSV/EBOV-GP expressing either green fluorescent protein or secreted Nano luciferase. Most modified vector constructs induced lower levels of protective antibodies than the parental VSV/EBOV-GP or a recombinant modified vaccinia virus Ankara vector encoding full-length EBOV-GP. However, the VSV/EBOV-GP(F88A) mutant was at least as immunogenic as the parental vaccine virus although it was highly propagation-restricted. This finding suggests that VSV-vectored vaccines need not be propagation-competent to induce a robust humoral immune response. However, VSV/EBOV-GP(F88A) rapidly reverted to a fully propagation-competent virus indicating that a single-point mutation is not sufficient to maintain the propagation-restricted phenotype.

Cellular kinases are crucial for the transcription/replication of many negative-strand RNA viruses and might serve as targets for antiviral therapy. In this study, a library comprising 80 kinase inhibitors was screened for antiviral activity against vesicular stomatitis virus (VSV), a prototype member of the family Rhabdoviridae . 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125), an inhibitor of eukaryotic elongation factor 2 (eEF2) kinase, significantly inhibited entry of single-cycle VSV encoding a luciferase reporter. Treatment of virus particles had only minimal effect on virus entry, indicating that the compound primarily acts on the host cell rather than on the virus. Accordingly, resistant mutant viruses were not detected when the virus was passaged in the presence of the drug. Unexpectedly, NH125 led to enhanced, rather than reduced, phosphorylation of eEF2, however, it did not significantly affect cellular protein synthesis. In contrast, NH125 revealed lysosomotropic features and showed structural similarity with N -dodecylimidazole, a known lysosomotropic agent. Related alkylated imidazolium compounds also exhibited antiviral activity, which was critically dependent on the length of the alkyl group. Apart from VSV, NH125 inhibited infection by VSV pseudotypes containing the envelope glycoproteins of viruses that are known to enter cells in a pH-dependent manner, i.e. avian influenza virus (H5N1), Ebola virus, and Lassa virus. In conclusion, we identified an alkylated imidazolium compound which inhibited entry of several viruses not because of the previously postulated inhibition of eEF2 kinase but most likely because of its lysosomotropic properties.

Background: To compare anti-VEGF treatments for macular disease in terms of costs and clinical outcomes., Methods: We identified patients suffering from macular disease and treated either with aflibercept, ranibizumab or both at the largest public eye clinic in Switzerland between January 1st and December 31st 2016 who were insured in one of the two participating health insurance companies. Clinical data were extracted from the electronic health record system. The health insurers provided the health claim costs for the ophthalmologic care and the total health care costs of each patient in the observation period. Using multivariate regression models, we assessed the monthly ophthalmologic and the monthly total costs of patients with no history of switching (ranibizumab vs. aflibercept), patients with a history of switching from ranibizumab to aflibercept, patients switching during the observation period and a miscellaneous group. We examined baseline differences in age, proportion of males, visual acuity (letters), central retinal thickness (CRT) and treatment history before entering the study. We investigated treatment intensity and compared the changes in letters and CRT., Results: The analysis involved 488 eyes (361 patients), 182 on ranibizumab treatment, and 63 on aflibercept treatment, 160 eyes with a history of switching from ranibizumab to aflibercept, and 45 switchers during follow-up and 38 eyes of the miscellaneous group. Compared to ranibizumab, monthly costs of ophthalmologic treatment were slightly higher for aflibercept treatment + 175.0 CHF (95%CI: 1.5 CHF to 348.3 CHF; p = 0.048) as were the total monthly costs + 581.0 CHF (95%CI: 159.5 CHF to 1002.4 CHF; p = 0.007). Compared to ranibizumab, the monthly treatment intensity with aflibercept was similar (+ 0.057 injections/month (95%CI -0.023 to 0.137; p = 0.162), corresponding to a projected annual number of 5.4 injections for ranibizumab vs. 6.1 injections for aflibercept. During follow-up, visus dropped by 0.7 letters with ranibizumab and increased by 0.6 letters with aflibercept (p = 0.243). CRT dropped by - 14.9 μm with ranibizumab and by - 19.5 μm with aflibercept (p = 0.708). The monthly costs of all other groups examined were higher., Conclusion: These real-life data show that aflibercept treatment is equally expensive, and clinical outcomes between the two drugs are similar.

Two novel influenza A-like viral genome sequences have recently been identified in Central and South American fruit bats and provisionally designated "HL17NL10" and "HL18NL11." All efforts to isolate infectious virus from bats or to generate these viruses by reverse genetics have failed to date. Recombinant vesicular stomatitis virus (VSV) encoding the hemagglutinin-like envelope glycoproteins HL17 or HL18 in place of the VSV glycoprotein were generated to identify cell lines that are susceptible to bat influenza A-like virus entry. More than 30 cell lines derived from various species were screened but only a few cell lines were found to be susceptible, including Madin-Darby canine kidney type II (MDCK II) cells. The identification of cell lines susceptible to VSV chimeras allowed us to recover recombinant HL17NL10 and HL18NL11 viruses from synthetic DNA. Both influenza A-like viruses established a productive infection in MDCK II cells; however, HL18NL11 replicated more efficiently than HL17NL10 in this cell line. Unlike conventional influenza A viruses, bat influenza A-like viruses started the infection preferentially at the basolateral membrane of polarized MDCK II cells; however, similar to conventional influenza A viruses, bat influenza A-like viruses were released primarily from the apical site. The ability of HL18NL11 or HL17NL10 viruses to infect canine and human cells might reflect a zoonotic potential of these recently identified bat viruses., Competing Interests: The authors declare no conflict of interest.

Rabies is a highly fatal zoonotic disease which is primarily caused by rabies virus (RABV) although other members of the genus Lyssavirus can cause rabies as well. As yet, 14 serologically and genetically diverse lyssaviruses have been identified, mostly in bats. To assess the quality of rabies vaccines and immunoglobulin preparations, virus neutralization tests with live RABV are performed in accordance with enhanced biosafety standards. In the present work, a novel neutralization test is presented which takes advantage of a modified vesicular stomatitis virus (VSV) from which the glycoprotein G gene has been deleted and replaced by reporter genes. This single-cycle virus was trans-complemented with RABV envelope glycoprotein. Neutralization of this pseudotype virus with RABV reference serum or immune sera from vaccinated mice showed a strong correlation with the rapid fluorescent focus inhibition test (RFFIT). Importantly, pseudotype viruses containing the envelope glycoproteins of other lyssaviruses were neutralized by reference serum to a significantly lesser extent or were not neutralized at all. Taken together, a pseudotype virus system has been successfully developed which allows the safe, fast, and sensitive detection of neutralizing antibodies directed against different lyssaviruses., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of one of the most devastating and economically significant viral disease of pigs worldwide. The vaccines currently available on the market elicit only limited protection. Recombinant vesicular stomatitis virus (VSV) replicon particles (VRP) have been used successfully to induce protection against influenza A virus (IAV) in chickens and bluetongue virus in sheep. In this study, VSV VRP expressing the PRRSV envelope proteins GP5, M, GP4, GP3, GP2 and the nucleocapsid protein N, individually or in combination, were generated and evaluated as a potential vector vaccine against PRRSV infection. High level expression of the recombinant PRRSV proteins was demonstrated in cell culture. However, none of the PRRSV antigens expressed from VRP, with the exception of the N protein, did induce any detectable antibody response in pigs before challenge infection with PRRSV. After challenge however, the antibody responses against GP5, GP4 and GP3 appeared in average 2 weeks earlier than in pigs vaccinated with the empty control VRP. No reduction of viremia was observed in the vaccinated group compared with the control group. When pigs were co-vaccinated with VRP expressing IAV antigens and VRP expressing PRRSV glycoproteins, only antibody responses to the IAV antigens were detectable. These data show that the VSV replicon vector can induce immune responses to heterologous proteins in pigs, but that the PRRSV envelope proteins expressed from VSV VRP are poorly immunogenic. Nevertheless, they prime the immune system for significantly earlier B-cell responses following PRRSV challenge infection.

Unlabelled: The envelope of influenza A viruses contains two large antigens, hemagglutinin (HA) and neuraminidase (NA). Conventional influenza virus vaccines induce neutralizing antibodies that are predominantly directed to the HA globular head, a domain that is subject to extensive antigenic drift. Antibodies directed to NA are induced at much lower levels, probably as a consequence of the immunodominance of the HA antigen. Although antibodies to NA may affect virus release by inhibiting the sialidase function of the glycoprotein, the antigen has been largely neglected in past vaccine design. In this study, we characterized the protective properties of monospecific immune sera that were generated by vaccination with recombinant RNA replicon particles encoding NA. These immune sera inhibited hemagglutination in an NA subtype-specific and HA subtype-independent manner and interfered with infection of MDCK cells. In addition, they inhibited the sialidase activities of various influenza viruses of the same and even different NA subtypes. With this, the anti-NA immune sera inhibited the spread of H5N1 highly pathogenic avian influenza virus and HA/NA-pseudotyped viruses in MDCK cells in a concentration-dependent manner. When chickens were immunized with NA recombinant replicon particles and subsequently infected with low-pathogenic avian influenza virus, inflammatory serum markers were significantly reduced and virus shedding was limited or eliminated. These findings suggest that NA antibodies can inhibit virus dissemination by interfering with both virus attachment and egress. Our results underline the potential of high-quality NA antibodies for controlling influenza virus replication and place emphasis on NA as a vaccine antigen., Importance: The neuraminidase of influenza A viruses is a sialidase that acts as a receptor-destroying enzyme facilitating the release of progeny virus from infected cells. Here, we demonstrate that monospecific anti-NA immune sera inhibited not only sialidase activity, but also influenza virus hemagglutination and infection of MDCK cells, suggesting that NA antibodies can interfere with virus attachment. Inhibition of both processes, virus release and virus binding, may explain why NA antibodies efficiently blocked virus dissemination in vitro and in vivo. Anti-NA immune sera showed broader reactivity than anti-HA sera in hemagglutination inhibition tests and demonstrated cross-subtype activity in sialidase inhibition tests. These remarkable features of NA antibodies highlight the importance of the NA antigen for the development of next-generation influenza virus vaccines., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)