Measuring the intangible resources caregivers need to provide nurturing care during the complementary feeding period: a scoping review in low- and lower-middle-income countries.

OBJECTIVE: Caregivers require tangible (e.g. food and financial) and intangible resources to provide care to ensure child health, nutrition and development. Intangible resources include beliefs and knowledge, education, self-efficacy, perceived physical health, mental health, healthy stress levels, social support, empowerment, equitable gender attitudes, safety and security and time sufficiency. These intangible caregiver resources are included as intermediate outcomes in nutrition conceptual frameworks yet are rarely measured as part of maternal and child nutrition research or evaluations. To facilitate their measurement, this scoping review focused on understudied caregiver resources that have been measured during the complementary feeding period in low- and lower-middle-income countries. DESIGN: We screened 9,232 abstracts, reviewed 277 full-text articles and included 163 articles that measured caregiver resources related to complementary feeding or the nutritional status of children 6 months to 2 years of age. RESULTS: We identified measures of each caregiver resource, though the number of measures and quality of descriptions varied widely. Most articles (77 %) measured only one caregiver resource, mental health (n 83) and social support (n 54) most frequently. Psychometric properties were often reported for mental health measures, but less commonly for other constructs. Few studies reported adapting measures for specific contexts. Existing measures for mental health, equitable gender attitudes, safety and security and time sufficiency were commonly used; other constructs lacked standardised measures. CONCLUSIONS: Measurement of caregiver resources during the complementary feeding period is limited. Measuring caregiver resources is essential for prioritising caregivers and understanding how resources influence child care, feeding and nutrition.

Quantifying the impact of initial RNA primer length on nucleotide addition by RNA polymerase I.

Transient state kinetic studies of eukaryotic DNA-dependent RNA polymerases (Pols) in vitro provide quantitative characterization of enzyme activity at the level of individual nucleotide addition events. Previous work revealed heterogeneity in the rate constants governing nucleotide addition by yeast RNA polymerase I (Pol I) for each position on a template DNA. In contrast, the rate constants that described nucleotide addition by yeast RNA polymerase II (Pol II) were more homogeneous. This observation led to the question, what drives the variability of rate constants governing RNA synthesis by Pol I? Are the kinetics of nucleotide addition dictated by the position of the nascent RNA within the polymerase or by the identity of the next encoded nucleotide? In this study, we examine the impact of nucleotide position (i.e. nascent RNA primer length) on the rate constants governing nine sequential nucleotide addition events catalyzed by Pol I. The results reveal a conserved trend in the observed rate constants at each position for all primer lengths used, and highlight that the 9-nucleotide, or 9-mer, RNA primer provides the fastest observed rate constants. These findings suggest that the observed heterogeneity of rate constants for RNA synthesis by Pol I in vitro is driven primarily by the template sequence.

The effects of SLICE®- and ivermectin-contaminated sediment on avoidance behaviour and oxygen consumption in marine benthic invertebrates.

Pest management strategies to reduce sea lice infestations in the salmon aquaculture industry include in-feed treatments with ivermectin (IVM) and SLICE® (active ingredient [AI] emamectin benzoate [EMB]), which can result in local contamination of the environment. These compounds partition to sediments, have moderate persistence, and may pose a risk to non-target benthic organisms. The sub-lethal effects of EMB, IVM and a combination of both (EMB/IVM) on the benthic amphipod Eohaustorius estuarius and polychaete Nereis virens at environmentally relevant sediment concentrations were examined in subchronic exposures (28-30-d). E. estuarius avoided sediment containing >50 µg/kg IVM alone and in combination with EMB. N. virens avoided sediment with >50 µg/kg IVM and >0.5 µg/kg EMB/IVM and exhibited impaired burrowing and locomotory behaviour with both treatments. Oxygen consumption was significantly decreased in E. estuarius (up to 50% compared to controls) and increased in N. virens (by âˆ¼ 200%) when exposed to EMB, IVM and EMB/IVM at concentrations <5 µg/kg. IVM, SLICE® and combination exposures at environmentally relevant concentrations caused adverse effects in E. estuarius and N. virens which could significantly alter organism fitness near salmon aquaculture operations.

The humanistic and economic burden of work-related musculoskeletal pain: a cross-sectional survey of workers in the United Kingdom.

OBJECTIVE: The aim of this study was to evaluate the impact of work-related musculoskeletal (MSK) lower body pain on health-related quality of life (HRQoL) and work productivity in a large sample of workers in the United Kingdom, as well as evaluating the potential economic impact of MSK pain. METHODS: Participants with self-reported work-related MSK pain were recruited from an online panel maintained by a third party (Qualtrics LLC). Participants completed three validated instruments online: the Brief Pain Inventory (BPI), the Assessment of Quality of Life Instrument (AQoL-4D), and the 6-item Work Productivity and Activity Impairment Questionnaire (WPAI). Sociodemographic details, work patterns and healthcare resource utilisation were also reported. One-way analysis of variance (ANOVA) and t-tests were used to explore differences between variables. Linear regression was applied to determine the impact of work-related MSK pain on HRQoL. RESULTS: All 1035 recruited participants completed the survey (57.4% female; mean age 43.4 years). Participants reported spending all (25.2%) or most (53%) of their time at work on their feet. Mean pain severity was 4.63 (standard deviation: 2.07); mean pain interference was 4.37 (2.49). There was a linear relationship between length of shift, time on feet and pain. Mean AQoL-4D scores were 0.609 (0.254). A mean of 4.12 h was lost per week due to pain. Absenteeism (last 7 days) was 9.5% (20.7%), and presenteeism 33.3% (24.9%). An average 1.55 visits were made to family practitioners (total cost: £19,866) and 1 hospital visit (£37,320) due to work-related MSK pain. CONCLUSION: This study demonstrated that work-related lower body pain has a significant impact in terms of individual HRQoL and as an economic societal burden.

A novel immuno-molecular strategy for the detection of Streptococcus pneumoniae serotypes in human cerebrospinal and middle ear fluids.

Streptococcus pneumoniae is one of the most common microorganisms causing acute otitis media (AOM) in children. While bacterial culture of middle ear fluid (MEF) is the gold standard to detect the etiological organisms, several host and pathogen factors impact the survival of the organisms resulting in false negatives. To overcome this limitation, we have developed and validated an innovative multiplex immuno-molecular assay to screen and detect the S. pneumoniae 15-valent pneumococcal conjugate vaccine (PCV15; STs 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) vaccine serotypes in MEF. This novel in vitro approach involves two-step testing. First, the MEF specimens were tested for highly conserved pneumococcal genes, autolysin, lytA, and pneumolysin, ply using direct PCR to identify pneumococcus positive specimens. The pneumococcus positive specimens were screened for the presence of vaccine serotype specific pneumococcal polysaccharides using a 15-plex Pneumococcal Antigen Detection (PAD) assay, with specific capture and detection monoclonal antibodies. Due to the lack of availability of MEF samples, cerebrospinal fluid (CSF) was used as the surrogate matrix for the development and validation of the PCR-PAD assays. The PCR and PAD assays were separately evaluated for sensitivity and specificity. Subsequently, the PCR-PAD assays were cross-validated with human MEF samples (n = 39) which were culture confirmed to contain relevant bacterial strains. The combined PCR-PAD assays demonstrated high rate of agreement 94.9% (95% CI; 82.7, 99.4%) with historical Quellung serotype data of these MEF samples. This novel PCR-PAD assay demonstrates the feasibility of combining molecular and immunological assays to screen and identify PCV15 pneumococcal vaccine serotypes in AOM clinical samples.

Introduction of a Maternal-Fetal Medicine Tele-Ultrasound Program in Rural Alberta.

OBJECTIVES: We established a program of Maternal-Fetal Medicine (MFM) telemedicine that is safe and acceptable. Since December 2019, a multi-disciplinary team has been planning this quality improvement project. METHODS: We performed a pilot study to investigate the feasibility of using telemedicine and tele-ultrasound to enable prompt MFM consultations for patients in remote locations. We began with the training of sonographers followed by implementation in a small pilot. Interim analysis of the acceptability and feasibility of the program was done through patient surveys, images audit, and review of neonatal outcomes. RESULTS: Our background epidemiologic data showed that in Alberta, between 2017 and 2022, 460 patients travelled >6 hours, and 5038 travelled >2 hours from home to reach their site of birth. Patients were appropriately triaged to delivery/consultation at the tertiary level center based on diagnosis/suspicion of anomalies, such as abnormally invasive placenta, intrauterine growth restriction, hydrops, and partial agenesis of the corpus callosum, all of which were confirmed postdelivery. There was no neonatal mortality, and the single stillbirth was related to an unpreventable peri-viable co-twin demise. The patient survey demonstrated that for >85% of respondents the program reduced costs and stress. Ultrasound image audit found improvement and consistency in image quality after 3 months of training combined with supervision. CONCLUSION: MFM telemedicine is feasible and can be safe with adequate supervision. Additional support and resources are needed to scale and spread this quality improvement initiative.

#Cheers: An Examination of User-Generated Alcohol Advertising on Instagram.

Background: Alcohol marketing is a known risk factor for youth drinking. The growth in digital marketing has generated a new form of alcohol advertisement in which brands solicit and/or share consumer-generated or user-generated content. Objectives: The current study investigates the prevalence of UGC alcohol advertising on social media and examines the content of UGC advertising to determine potential violations of current regulatory guidelines. Results: The Instagram accounts of 20 Nova Scotia breweries were monitored for the month of July 2021. User-generated content made up a substantial portion (41%) of all Instagram stories (n = 1531), and there were 321 violations of the Canadian Radio-television and Telecommunications Commission code for broadcast advertising of alcoholic beverage. Ten percent of violations encouraged consumption, 59% depicted irresponsible use, 14% appealed to youth, 14% associated alcohol with activities requiring a degree of skill or care, 2.5% associated alcohol with social or personal success. Conclusions/Importance: These findings indicate that UGC is a commonly used marketing strategy among alcohol producers and the current self-regulatory system is insufficient in preventing advertising that appeals to youth and exacerbates a culture of immoderate consumption.

RNA Polymerase I Is Uniquely Vulnerable to the Small-Molecule Inhibitor BMH-21.

Cancer cells require robust ribosome biogenesis to maintain rapid cell growth during tumorigenesis. Because RNA polymerase I (Pol I) transcription of the ribosomal DNA (rDNA) is the first and rate-limiting step of ribosome biogenesis, it has emerged as a promising anti-cancer target. Over the last decade, novel cancer therapeutics targeting Pol I have progressed to clinical trials. BMH-21 is a first-in-class small molecule that inhibits Pol I transcription and represses cancer cell growth. Several recent studies have uncovered key mechanisms by which BMH-21 inhibits ribosome biosynthesis but the selectivity of BMH-21 for Pol I has not been directly measured. Here, we quantify the effects of BMH-21 on Pol I, RNA polymerase II (Pol II), and RNA polymerase III (Pol III) in vitro using purified components. We found that BMH-21 directly impairs nucleotide addition by Pol I, with no or modest effect on Pols II and III, respectively. Additionally, we found that BMH-21 does not affect the stability of any of the Pols' elongation complexes. These data demonstrate that BMH-21 directly exploits unique vulnerabilities of Pol I.

Development and Validation of a Sensitive and Robust Multiplex Antigen Capture Assay to Quantify Streptococcus pneumoniae Serotype-Specific Capsular Polysaccharides in Urine.

Streptococcus pneumoniae is a major cause of community-acquired pneumonia (CAP) in young children, older adults, and those with immunocompromised status. Since the introduction of pneumococcal vaccines, the burden of invasive pneumococcal disease caused by vaccine serotypes (STs) has decreased; however, the effect on the burden of CAP is unclear, potentially due to the lack of testing for pneumococcal STs. We describe the development, qualification, and clinical validation of a high-throughput and multiplex ST-specific urine antigen detection (SSUAD) assay to address the unmet need in CAP pneumococcal epidemiology. The SSUAD assay is sensitive and specific to the 15 STs in the licensed pneumococcal conjugate vaccine V114 (STs 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) and uses ST-specific monoclonal antibodies for rapid and simultaneous quantification of the 15 STs using a Luminex microfluidics system. The SSUAD assay was optimized and qualified using healthy adult urine spiked with pneumococcal polysaccharides and validated using culture-positive clinical urine samples (n = 34). Key parameters measured were accuracy, precision, sensitivity, specificity, selectivity, and parallelism. The SSUAD assay met all prespecified validation acceptance criteria and is suitable for assessments of disease burden associated with the 15 pneumococcal STs included in V114. IMPORTANCE Streptococcus pneumoniae has more than 90 serotypes capable of causing a range of disease manifestations, including otitis media, pneumonia, and invasive diseases, such as bacteremia or meningitis. Only a minority (<10%) of pneumococcal diseases are bacteremic with known serotype distribution. Culture and serotyping of respiratory specimens are neither routine nor reliable. Hence, the serotype-specific disease burden of the remaining (>90%) noninvasive conditions is largely unknown without reliable laboratory techniques. To address this need, a 15-plex urine antigen detection assay was developed and validated to quantify pneumococcal serotype-specific capsular polysaccharides in urine. This assay will support surveillance to estimate the pneumococcal disease burden and serotype distribution in nonbacteremic conditions. Data obtained from this assay will be critical for understanding the impact of pneumococcal vaccines on noninvasive pneumococcal diseases and to inform the choice of pneumococcal serotypes for next-generation vaccines.

Level-loading a health system by transferring emergency department patients to a community hospital: Prospective cohort study.

BACKGROUND: Emergency department boarding and crowding lead to worse patient outcomes and patient satisfaction. OBJECTIVE: We describe the implementation of a program to transfer patients requiring medical admission from an academic emergency department to a community hospital's medical floor and analyze its effects on patient outcomes. METHODS: A prospective cohort study was performed. Data was collected on patient flow through the transfer program. Patient characteristics, boarding time in the emergency department, and hospital-based outcome measures were compared between patients in the transfer program who were successfully transferred to the community hospital and patients who were admitted to the academic medical center. RESULTS: 79 patients were successfully transferred to the community hospital between November 23, 2020 and August 5, 2021, resulting in 279 bed days in the community hospital. Successfully transferred patients experienced a statistically shorter ED boarding time (5.7 vs. 10.9 h, p < 0.0001), ED length of stay (10.5 vs 16.1 h, p < 0.0001), and hospital length of stay (3.5 vs 5.7 days, p < 0.0001) compared to patients initially referred to the transfer program who were admitted to the academic medical center. There were no reported adverse events during transfer, upgrades to the ICU within 24 h of admission, or inpatient deaths for patients who were transferred. CONCLUSION: We implemented an academic emergency department to partner community hospital transfer program that safely level-loads medical patients in a healthcare system.

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866.

COVID-19 Level-Loading: Transferring Emergency Department Patients to a Partner Academic Medical Center Within a Healthcare System.

COVID-19 continues to challenge bed capacity and the ability of hospitals to provide quality care for patients around the country. However, the COVID-19 pandemic at a given point in time does not impact all hospitals equally-even within a single healthcare system, one hospital may be caring for patients in the hallways, while another has available inpatient beds. Here, we demonstrate a program to level-load COVID-19 patients between 2 academic medical centers in a healthcare system by transferring patients at the time of admission from the emergency department of one institution directly to an inpatient bed of the other institution. Over 42 days, 50 patients were transferred which saved 432 bed-days at the home academic medical center without any adverse events during transfer or upgrades to the ICU within the first 24 hours of admission. Programs like this can expand a healthcare system's ability to allocate personnel and resources efficiently for patients and maximize the quality of care delivered even during a pandemic.

Do age-associated changes of voltage-gated sodium channel isoforms expressed in the mammalian heart predispose the elderly to atrial fibrillation?

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. The prevalence of the disease increases with age, strongly implying an age-related process underlying the pathology. At a time when people are living longer than ever before, an exponential increase in disease prevalence is predicted worldwide. Hence unraveling the underlying mechanics of the disease is paramount for the development of innovative treatment and prevention strategies. The role of voltage-gated sodium channels is fundamental in cardiac electrophysiology and may provide novel insights into the arrhythmogenesis of AF. Nav1.5 is the predominant cardiac isoform, responsible for the action potential upstroke. Recent studies have demonstrated that Nav1.8 (an isoform predominantly expressed within the peripheral nervous system) is responsible for cellular arrhythmogenesis through the enhancement of pro-arrhythmogenic currents. Animal studies have shown a decline in Nav1.5 leading to a diminished action potential upstroke during phase 0. Furthermore, the study of human tissue demonstrates an inverse expression of sodium channel isoforms; reduction of Nav1.5 and increase of Nav1.8 in both heart failure and ventricular hypertrophy. This strongly suggests that the expression of voltage-gated sodium channels play a crucial role in the development of arrhythmias in the diseased heart. Targeting aberrant sodium currents has led to novel therapeutic approaches in tackling AF and continues to be an area of emerging research. This review will explore how voltage-gated sodium channels may predispose the elderly heart to AF through the examination of laboratory and clinical based evidence.

Monitoring maternal near miss/severe maternal morbidity: A systematic review of global practices.

There is international interest in monitoring severe events in the obstetrical population, commonly referred to as maternal near miss or severe maternal morbidity. These events can have significant consequences for individuals in this population and further study can inform practices to reduce both maternal morbidity and mortality. Numerous surveillance systems exist but we lack a standardized approach. Given the current inconsistencies and the importance in monitoring these events, this study aimed to identify and compare commonly used surveillance methods. In June 2018, we systematically searched MEDLINE, EMBASE, and CINAHL using terms related to monitoring/surveillance and maternal near miss/severe maternal morbidity. We included papers that used at least three indicators to monitor for these events and collected data on specific surveillance methods. We calculated the rate of maternal near miss/severe maternal morbidity in hospitalization data obtained from the 2016 US National Inpatient Sample using five common surveillance methods. Of 18,832 abstracts, 178 papers were included in our review. 198 indicators were used in studies included in our review; 71.2% (n = 141) of these were used in <10% of included studies and only 6.1% (n = 12) were used in >50% of studies included in our review. Eclampsia was the only indicator that was assessed in >80% of included studies. The rate of these events in American hospitalization data varied depending on the criteria used, ranging from 5.07% (95% CI = 5.02, 5.11) with the Centers for Disease Control criteria and 7.85% (95% CI = 7.79, 7.91) using the Canadian Perinatal Surveillance System. Our review highlights inconsistencies in monitoring practices within and between developed and developing countries. Given the wide variation in monitoring approaches observed and the likely contributing factors for these differences, it may be more feasible for clinical and academic efforts to focus on standardizing approaches in developed and developing countries independently at this time. PROSPERO Registration: CRD42018096858.

Antenatal Diagnosis of Marginal and Velamentous Placental Cord Insertion and Pregnancy Outcomes.

OBJECTIVE: To evaluate the association between antenatal diagnosis of velamentous and marginal placental cord insertions with adverse perinatal outcomes of small-for-gestational-age (SGA) birth weight (less than the 5th percentile), caesarean birth, and perinatal mortality. METHODS: Using a diagnostic imaging database, we performed a cohort study of all consecutive singleton pregnancies (35,391), including 1,427 cases of marginal and 107 cases of velamentous cord insertion, delivered after 24 6/7 weeks of gestation between January 1, 2012, and December 31, 2015, at a single Canadian tertiary care center. Cases with placenta previa, vasa previa, no documented cord insertion, or fetal anomalies were excluded. RESULTS: In the overall cohort, the rate of birth weight less than the 5th percentile was 5.2%, the rate of cesarean delivery was 27.1%, and the rate of perinatal mortality was 0.24%. Velamentous cord insertion was associated with SGA (relative risk [RR] 2.19, 95% CI 1.28-3.74). This persisted after controlling for smoking during pregnancy, diabetes, and hypertension (adjusted odds ratio [aOR] 1.98, 95% CI 1.03-3.84). Velamentous cord insertion was also associated with an increased risk of caesarean birth (RR=1.38, 95% CI=1.08-1,77) and perinatal death (1.87%, RR 8.15, 95% CI 2.02-32.8), a relationship that persisted after controlling for smoking during pregnancy, diabetes, and hypertension (aOR 1.53, 95% CI 1.01-2.32). Marginal cord insertion was not associated with birth weight less than the 5th percentile (RR 1.23, 95% CI 1.00-1.51), cesarean delivery (RR 1.01, 95% CI 0.92-1.10), or perinatal death (RR 1.53, 95% CI 0.62-3.78). CONCLUSION: Antenatal diagnosis of velamentous placental cord insertion is associated with birth weight less than the 5th percentile.

Advanced Heart Failure Treatment Modalities and Hospice Care: The Need for High Level Care Coordination.

Advanced heart failure therapies such as ventricular assist devices and home inotrope use are becoming more common. Technology advances as well as increased indications for use of such therapies is leading to a higher percentage of patients with end-stage heart failure receiving these therapies at end of life. We present a case of a young man with dilated cardiomyopathy who undergoes advanced cardiac care in the setting of progressively declining cardiac function. Our case outlines the importance of acute care, palliative care, and hospice services being coordinated prior to and during acute-care services to provide goal-concordant and expeditious care. With advancing medical therapies for heart disease, increased coordination and collaboration of services are needed, particularly between hospice and acute-care services.

Palliative care in end-stage valvular heart disease.

Valvular heart disease (VHD), particularly aortic valve disease, is prevalent with increasing incidence. When surgery is not possible, or when risks outweigh benefits, percutaneous treatment options may offer effective alternatives. However, procedures may not always go as planned, and frail patients or those whose symptoms are caused by other comorbidities may not benefit from valve intervention at all. Significant effort should be made to assess frailty, comorbidities and patient goals prior to intervention. Palliative care (PC) should play a critical role in the care of patients with severe valve disease. PC is specialised medical care that aims to optimise health-related quality of life by managing symptoms and clarifying patient values and goals of care. It should be implemented at the time of diagnosis and continue throughout the disease course. Because of the paucity of studies dedicated to the provision of PC to patients with advanced VHD, further research is needed.