Systematic review: effect of probiotics on antibiotic-induced microbiome disruption.

The effectiveness of probiotics in preventing or reversing antibiotic-induced microbiome disruption remains uncertain, and claims of microbiome restoration to its pre-antibiotic state may be overestimated. In this review, we aimed to assess the efficacy of probiotics in preventing or ameliorating disruptions in microbiome composition and function induced by antibiotic treatment. We searched Medline, Embase, and CENTRAL for randomised controlled and non-randomised trials. Participants were individuals of any age who were on systemic antibiotics with a low risk of baseline dysbiosis. The intervention consisted of probiotics during or after antibiotic treatment, compared to placebo, alternative interventions, or no intervention. Outcomes included microbiome composition and diversity analysed using high-throughput molecular methods, alongside microbial function and resistome assessments. Seven studies, reported in eight papers, were reviewed. One study showed probiotics counteracting antibiotic-induced diversity changes, another showed exacerbation of these changes, and four others showed no effect. Effects on taxa abundance ranged from mitigating dysbiosis to selective modulation, no effect, or delayed recovery. One study observed no impact on the resistome, while another reported an increase in antibiotic resistance genes. In conclusion, heterogeneous results preclude a definitive conclusion on the effectiveness of any specific probiotic in restoring antibiotic-exposed microbiomes. For a clearer understanding, future research should be more standardised and long-term, employing advanced methods, such as 16S rRNA gene sequencing and metagenomic sequencing. These studies should strive to include larger, diverse populations to enhance generalisability and clearly define what constitutes a healthy microbiome. Finally, linking changes in the microbiome to specific clinical outcomes is essential for clinical decision making. PROSPERO registration number: CRD42023446214.

Epidural Spinal Cord Stimulation for Spinal Cord Injury in Humans: A Systematic Review.

(1) Background: Spinal cord injury (SCI) represents a major health challenge, often leading to significant and permanent sensorimotor and autonomic dysfunctions. This study reviews the evolving role of epidural spinal cord stimulation (eSCS) in treating chronic SCI, focusing on its efficacy and safety. The objective was to analyze how eSCS contributes to the recovery of neurological functions in SCI patients. (2) Methods: We utilized the PRISMA guidelines and performed a comprehensive search across MEDLINE/PubMed, Embase, Web of Science, and IEEE Xplore databases up until September 2023. We identified studies relevant to eSCS in SCI and extracted assessments of locomotor, cardiovascular, pulmonary, and genitourinary functions. (3) Results: A total of 64 studies encompassing 306 patients were identified. Studies investigated various stimulation devices, parameters, and rehabilitation methods. Results indicated significant improvements in motor function: 44% of patients achieved assisted or independent stepping or standing; 87% showed enhanced muscle activity; 65% experienced faster walking speeds; and 80% improved in overground walking. Additionally, eSCS led to better autonomic function, evidenced by improvements in bladder and sexual functions, airway pressures, and bowel movements. Notable adverse effects included device migration, infections, and post-implant autonomic dysreflexia, although these were infrequent. (4) Conclusion: Epidural spinal cord stimulation is emerging as an effective and generally safe treatment for chronic SCI, particularly when combined with intensive physical rehabilitation. Future research on standardized stimulation parameters and well-defined therapy regimens will optimize benefits for specific patient populations.

Factors contributing to a coronavirus disease 2019 (COVID-19) outbreak on a mixed medical-surgical unit in a Canadian acute-care hospital.

Objective: To identify preventable factors that contribute to the cross transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to patients in healthcare facilities. Design: A case-control study was conducted among inpatients on a coronavirus disease 2019 (COVID-19) outbreak unit. Setting: This study was conducted in a medical-surgical unit of a tertiary-care hospital in Nova Scotia in May 2021. Patients: Patients hospitalized on the unit for at least 12 hours and healthcare workers (HCW) working on the unit within 2 weeks of outbreak declaration were included. Methods: Risk factors for SARS-CoV-2 infection were analyzed using simple and multiple logistic regression. Whole-genome sequencing (WGS) was performed to identify SARS-CoV-2 strain relatedness. Network analysis was used to describe patient accommodation. Results: SARS-CoV-2 infections were identified in 21 patients (29.6%) and 11 HCWs (6.6%). WGS data revealed 4 distinct clades of related sequences. Several factors likely contributed to the outbreak, including failure to identify SARS-CoV-2, a largely incomplete or unvaccinated population, and patient wandering behaviors. The most significant risk factor for SARS-CoV-2 infection was room sharing with an infectious patient, which was the only factor that remained statistically significant following multivariate analysis (odds ratio [OR], 9.2l; 95% confidence interval [CI], 2.04-41.67; P = .004). Conclusions: This outbreak likely resulted from admission of 2 patients with COVID-19, with subsequent transmissions to 17 patients and 11 staff. WGS and bioinformatics analyses were critical to identifying previously unrecognized nosocomial transmissions of SARS-CoV-2. This study supports strategies to reduce nosocomial transmissions of SARS-CoV-2, such as single-patient rooms, promotion of COVID-19 vaccination, and infection prevention and control measures including management of wandering behaviors.

Ultrafast laser inscribed waveguides in tailored fluoride glasses: an enabling technology for mid-infrared integrated photonics devices.

Zirconium fluoride (ZBLAN) glass, the standard material used in fiber-based mid-infrared photonics, has been re-designed to enable the fabrication of high index-contrast low-loss waveguides via femtosecond laser direct writing. We demonstrate that in contrast to pure ZBLAN, a positive index change of close to 10-2 can be induced in hybrid zirconium/hafnium (Z/HBLAN) glasses during ultrafast laser inscription and show that this can be explained by an electron cloud distortion effect that is driven by the existence of two glass formers with contrasting polarizability. High numerical aperture (NA) type-I waveguides that support a well confined 3.1 µm wavelength mode with a mode-field diameter (MFD) as small as 12 µm have successfully been fabricated. These findings open the door for the fabrication of mid-infrared integrated photonic devices that can readily be pigtailed to existing ZBLAN fibers.

A Retrospective Observational Study of Anticoagulation Practices in Critically ill Patients with Atrial Fibrillation Admitted to the Intensive Care Unit.

BACKGROUND: Atrial Fibrillation (AF) is the most common arrhythmia in critically ill patients. AF precipitates thromboembolic (TE) events. International guidelines recommend long-term anticoagulation for AF patients dependent upon the risk of TE versus major bleeding events. The CHA2DS2VASc and HAS-BLED scores are used to calculate these risks, but have not been validated in intensive care. Little is known about the risk/benefit ratio of prescribing anticoagulation to patients with AF in the intensive care setting. METHODS: This observational study included patients who were admitted to intensive care and had AF episodes during admission. We aimed to 1) describe the anticoagulation strategies used in critically ill patients with AF, 2) determine the percentage of patients who received guideline-compliant anticoagulation and 3) compare anticoagulation strategies in patients with new onset AF (NOAF) and known AF. Demographic data was extracted from electronic health records. Therapeutic anticoagulation prescribed during AF episodes and outcomes were collected. CHA2DS2VASc and HAS-BLED scores were calculated and correlated with TE and bleeding events. RESULTS: The incidence of AF in our cohort was 13.8%. Anticoagulation was administered in 34.0% of patients. Anticoagulation use did not affect morbidity or mortality outcomes. Patients with pre-existing AF were anticoagulated more often compared to patients with NOAF. CHA2DS2VASc scores and TE events, and HAS-BLED scores and bleeding events did not correlate well. CONCLUSION: AF is common in critical care. Current guidelines on anticoagulation in AF may not be directly transferable to the critical care setting.

Risk factors associated with poorer experiences of end-of-life care and challenges in early bereavement: Results of a national online survey of people bereaved during the COVID-19 pandemic.

BACKGROUND: Experiences of end-of-life care and early bereavement during the COVID-19 pandemic are poorly understood. AIM: To identify clinical and demographic risk factors for sub-optimal end-of-life care and pandemic-related challenges prior to death and in early bereavement, to inform clinical practice, policy and bereavement support. DESIGN: Online national survey of adults bereaved in the UK (deaths between 16 March 2020 and 2 January 2021), recruited via media, social media, national associations and organisations. SETTING/PARTICIPANTS: 711 participants, mean age 49.5 (SD 12.9, range 18-90). 628 (88.6%) were female. Mean age of the deceased was 72.2 (SD 16.1, range miscarriage to 102 years). 311 (43.8%) deaths were from confirmed/suspected COVID-19. RESULTS: Deaths in hospital/care home increased the likelihood of poorer experiences at the end of life; for example, being unable to visit or say goodbye as wanted (p < 0.001). COVID-19 was also associated with worse experiences before and after death; for example, feeling unsupported by healthcare professionals (p < 0.001), social isolation/loneliness (OR = 0.439; 95% CI: 0.261-0.739), and limited contact with relatives/friends (OR = 0.465; 95% CI: 0.254-0.852). Expected deaths were associated with a higher likelihood of positive end-of-life care experiences. The deceased being a partner or child also increased the likelihood of positive experiences, however being a bereaved partner strongly increased odds of social isolation/loneliness, for example, OR = 0.092 (95% CI: 0.028-0.297) partner versus distant family member. CONCLUSIONS: Four clear risk factors were found for poorer end-of-life care and pandemic-related challenges in bereavement: place, cause and expectedness of death, and relationship to the deceased.

Improving the accuracy of retrieved cardiac electrical conductivities.

Accurate values for the six cardiac conductivities of the bidomain model are crucial for meaningful electrophysiological simulations of cardiac tissue and are yet to be achieved. A two-stage optimisation process is used to retrieve the cardiac conductivities from cardiac potentials measured on a multi-electrode array-the first stage simultaneously fits all six conductivities, and the second stage fits a subset of the conductivities (intracellular conductivities), while holding the remainder of the conductivities (extracellular conductivities) constant. Previous studies have shown that the intracellular conductivities are retrieved to a lesser degree of accuracy than extracellular conductivities. This study tests the proposition that there exists a relationship between the extracellular and intracellular conductivities during the second stage of the optimisation that affects the accuracy of the retrieved intracellular conductivities. A measure to quantify this relationship is developed using polynomial chaos. The results show that a significant relationship does exist, and thus any errors in the extracellular conductivities are magnified in the retrieved intracellular conductivities. Thus, it is suggested that future protocols for retrieving conductivities incorporate the uncertainty in the extracellular conductivities.

Impact of nutritional status/risk and post-operative nutritional management on clinical outcomes in patients undergoing gastrointestinal surgery: a prospective observational study.

BACKGROUND: Malnutrition is prevalent in patients undergoing gastrointestinal (GI) surgery and has been linked to adverse outcomes. The present study aimed to determine the association between early post-operative nutritional status/risk, post-operative nutritional management and clinical outcomes. METHODS: A prospective observational study was conducted in GI surgical patients with a minimum 3-day post-operative length of stay (LOS). Data on patient demographics, nutritional status/risk, post-operative nutritional management and clinical outcomes were collected. Four markers of nutritional status and risk were assessed: preoperative weight loss, nutrition risk, malnutrition status and hand grip strength. Clinical outcomes included: post-operative LOS, complication and readmissions rates. Multivariate linear and logistic regression were used to test for associations with clinical outcomes. RESULTS: One hundred and fifteen patients (55% female) with mean (SD) age of 60.8 (16.2) years were included. Median (IQR) post-operative LOS was 8.0 days (4.5-11.5), 37% of participants developed at least one complication post-operatively and 24% were readmitted within 30-days of discharge. Mean number of nil-by mouth (NBM) days post-operatively was 0.7 (1.2) and the average time to commence feeding was 3.3 (2.2) days after surgery. Poor nutritional status/risk between days 3-5 post-operatively assessed through all four markers was associated with longer post-operative LOS (all P < 0.05). No association was found between number of NBM days, time to feeding and clinical outcomes. CONCLUSION: Poor early post-operative nutritional status/risk is associated with longer post-operative LOS in patients undergoing GI surgery, which may facilitate simple identification of patients at high priority for nutritional intervention. The present study highlights the heterogeneity in post-operative nutritional management practices.

What evidence do economic evaluations in dental care provide? A scoping review.

OBJECTIVE: To collate the body of evidence in economic studies of different dental interventions. METHODS: Eligible English studies after 1980 were sourced from MEDLINE using MeSH terms and reviewed independently by 4 teams. Studies were grouped according to the type of dental intervention and their quality appraised using Drummond's Checklist. RESULTS: The number of dental economic studies increased from 1980 to 2016. A total of 91 studies were identified following the search strategy. Most studies were conducted in the United States (n=23), followed by Germany (n=14), Australia (n=10) and the United Kingdom (n=9). Preventative dental interventions comprised 37% of included studies (n=34), followed by restorative (n=14), prosthodontic (n=13) and periodontal interventions (n=12). Cost effectiveness analyses (n=68) comprise 75% of full economic evaluation (EE) studies, followed by cost-utility (n=17) and cost-benefit (n=6). Quality assessment checklists identified 60 studies as good, 23 as moderate and 8 as poor. Common methodological limitations were identified in EE studies. Comparison of studies identified trends and common findings within each dental intervention. CONCLUSION: High quality economic studies are important in directing resources and funding by policy makers. Standardisation of reporting outcome measures will improve the potential for interpretation and comparison between studies. Research adhering to recommended quality assessment checklists will improve the overall quality of evidence to better identify cost-effective treatments for different dental interventions.

Preventing transmission of bloodborne viruses from infected healthcare workers to patients: Summary of a new Canadian Guideline.

BACKGROUND: Although it is well documented that bloodborne viruses (BBVs), including human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) have been transmitted from patients to healthcare workers (HCWs), there has also been reported transmission from HCWs to patients during the provision of health care. With remarkable progress in infection prevention, diagnosis tools, treatment regimens and major improvements in guideline development methodology, there was a need to develop an evidence-based guideline to replace the 1998 Canadian consensus document for managing HCWs infected with BBVs. PURPOSE: This article summarizes the Canadian Guideline on the Prevention of Transmission of Bloodborne Viruses from Infected Healthcare Workers in Healthcare Settings. METHODS: A Guideline Development Task Group was established and key questions developed to inform the guideline content. Systematic reviews were conducted to evaluate the risk of HCW-to-patient transmission of HIV, HCV and HBV. Environmental scans were used to provide information on Expert Review Panels, disclosure of a HCW's serologic status and lookback investigations. Federal, provincial and territorial partners and key stakeholder organizations were consulted on the Guideline. RESULTS: The risk of HCW-to-patient BBV transmission was found to be negligible, except during exposure-prone procedures, where there is a risk that injury to the HCW may result in exposure of a patient's open tissues to the HCW's blood. Risk of ensuing transmission and the rate of transmission varied by BBV, and were lowest with HIV and highest with HBV. The Guideline provides key content, including recommendations regarding criteria to determine if a procedure is an exposure-prone procedure, management of HCWs infected with a BBV, including considerations for the HCW's fitness for practice, Expert Review Panels, HCW disclosure obligations and right to privacy and lookback investigations. CONCLUSION: This new Guideline provides a pan-Canadian approach for managing HCWs infected with a BBV, with recommendations related to preventing HCW-to-patient transmission of BBVs during the provision of care.

Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa.

These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.

Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. AIMS: To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. METHODS: We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. RESULTS: In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively). CONCLUSIONS: We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research.

Loss of PRP4K drives anoikis resistance in part by dysregulation of epidermal growth factor receptor endosomal trafficking.

Anoikis acts as a critical barrier to metastasis by inducing cell death upon cancer cell detachment from the extracellular matrix (ECM), thereby preventing tumor cell dissemination to secondary sites. The induction of anoikis requires the lysosomal-mediated downregulation of epidermal growth factor receptors (EGFRs) leading to termination of pro-survival signaling. In this study, we demonstrate that depletion of pre-mRNA splicing factor 4 kinase (PRP4K; also known as PRPF4B) causes dysregulation of EGFR trafficking and anoikis resistance. We also report a novel cytoplasmic localization of PRP4K at the late endosome, and demonstrate both nuclear and cytoplasmic localization in breast, lung and ovarian cancer tissue. Mechanistically, depletion of PRP4K leads to reduced EGFR degradation following cell detachment from the ECM and correlates with increased TrkB, vimentin and Zeb1 expression. As a result, PRP4K loss promotes sustained growth factor signaling and increased cellular resistance to anoikis in vitro and in a novel zebrafish xenotransplantation model of anoikis sensitivity, as well as increased metastasis in a mouse model of ovarian cancer. Thus, PRP4K may serve as a potential biomarker of anoikis sensitivity in ovarian and other epithelial cancers.

High Seroprevalence of Jamestown Canyon Virus among Deer and Humans, Nova Scotia, Canada.

Using residual serum samples from Nova Scotia, Canada, we found that 87.8% of tested deer and an estimated 20.6% of the human population were infected with Jamestown Canyon virus. Human seropositivity reached 48.2% in 1 region. This virus may be an underrecognized cause of disease in Nova Scotia.

Angiotensin receptor blocker use and gastro-oesophageal cancer survival: a population-based cohort study.

BACKGROUND: Angiotensin receptor blockers (ARBs; including candesartan, losartan, olmesartan and valsartan) are widely used to treat hypertension, heart failure and diabetic neuropathy. There is considerable pre-clinical evidence that ARBs can reduce cancer progression, particularly for gastric cancer. Despite this, epidemiological studies have yet to assess the impact of ARB use on gastro-oesophageal cancer survival. AIM: To investigate the association between post-diagnosis ARB use and gastro-oesophageal cancer survival. METHODS: We selected a cohort of patients with newly-diagnosed gastro-oesophageal cancer between 1998 and 2012 from English cancer registries. We linked to prescription and clinical records from the Clinical Practice Research Datalink, and to death records from the Office for National Statistics. We used time-dependant Cox-regression models to calculate hazard ratios (HRs) comparing gastro-oesophageal cancer-specific mortality between post-diagnosis ARB users and non-users, after adjusting for demographics, comorbidities and post-diagnosis aspirin or statin use. RESULTS: Our cohort included 5124 gastro-oesophageal cancer patients, of which 360 used ARBs, and 3345 died due to their gastro-oesophageal cancer during follow-up. After adjustment, ARB users had moderately lower risk of gastro-oesophageal cancer mortality than the non-users (HR = 0.83, 95% CI 0.71-0.98). There was evidence of a dose-response relationship with the lowest HRs observed among patients receiving at least 2 years of prescriptions (HR = 0.42, 95% CI 0.25-0.72). CONCLUSIONS: In this large population-based gastro-oesophageal cancer cohort, we found moderately reduced cancer-specific mortality among ARB users. However, confirmation in further independent epidemiological studies with sufficient staging information is required.