Late-Onset Hyponatremia in Premature Infants.

Late-onset hyponatremia (LOH) frequently affects premature infants 2 or more weeks of age due to inadequate sodium intake and excessive kidney loss. Late-onset hyponatremia typically occurs in infants who are physiologically stable and is defined as serum sodium of 132 mEq/L or less or between 133 and 135 mEq/L if receiving sodium supplementation. Recent evidence suggests that spot urine sodium levels may improve the recognition of LOH, as low levels of excreted urine reflect a total body sodium deficit and negative balance. Untreated LOH may result in poor somatic growth, neurodevelopmental delay, higher incidence of bronchopulmonary dysplasia, and more severe retinopathy of prematurity. The primary prevention of LOH is to maintain serum sodium between 135 and 145 mEq/L; however, there are currently no formal protocols guiding sodium supplementation. The purpose of this article is to present on overview of LOH pathophysiology and its effect on somatic growth, neurodevelopment outcomes, and other related sequelae. We further discuss general management strategies and describe a protocol for sodium supplementation that is presently undergoing an evaluation for effectiveness.

Mobility in Older Adults Receiving Maintenance Hemodialysis: A Qualitative Study.

RATIONALE & OBJECTIVE: For older adults, maintaining mobility is a major priority, especially for those with advanced chronic diseases like kidney failure. However, our understanding of the factors affecting mobility in older adults receiving maintenance hemodialysis is limited. STUDY DESIGN: Descriptive qualitative study. SETTING & PARTICIPANTS: Using purposive sampling, we recruited (1) persons aged≥60 years receiving maintenance hemodialysis; and (2) care partners (≥18 years) providing regular support to an older adult receiving hemodialysis. During a single in-person home visit, we assessed mobility using the Short Physical Performance Battery (SPPB) and conducted individual one-on-one interviews regarding important personal factors related to mobility. ANALYTICAL APPROACH: Descriptive statistics were used for demographic and SPPB data. Transcripts underwent thematic coding, informed by the International Classification of Function framework of mobility. We used conceptual content analysis to inductively extract themes and subthemes. RESULTS: We enrolled 31 older adults receiving hemodialysis (42% female, 68% Black) with a mean age of 73±8 years and mean dialysis vintage of 4.6±3.5 years; their mean SPPB score was 3.6±2.8 points. Among 12 care partners (75% female, 33% Black), the mean age was 54±16 years and mean SPPB score was 10.1±2.4 points. Major themes extracted were (1) mobility represents independence; (2) mobility is precarious; (3) limitations in mobility cause distress; (4) sources of encouragement and motivation are critical; and (5) adaptability is key. LIMITATIONS: Modest sample from single geographic area. CONCLUSIONS: For older adults receiving hemodialysis, mobility is severely limited and is often precarious in nature, causing distress. Older adults receiving hemodialysis and their care partners have identified sources of encouragement and motivation for mobility, and cite an adaptable mindset as important. Future studies should conceptualize mobility as a variable condition and build on this outlook of adaptability in the development of interventions.

The Impact of Care Partners on the Mobility of Older Adults Receiving Hemodialysis.

Rationale & Objective: Many older adults receiving hemodialysis have mobility limitations and rely on care partners, yet data are sparse regarding the support provided by care partners. Our aim was to examine how care partners support the mobility of an older adult receiving hemodialysis. Study Design: Qualitative study. Setting & Participants: Using purposive sampling, we recruited persons aged 60 years or more receiving maintenance hemodialysis and care partners aged 18 years or more who were providing support to an older adult receiving hemodialysis. We conducted in-person semi-structured interviews about mobility with each individual. Analytical Approach: We conducted descriptive and focused coding of interview transcripts and employed thematic analysis. Our outcome was to describe perceived mobility supports provided by care partners using qualitative themes. Results: We enrolled 31 older adults receiving hemodialysis (42% women, 68% Black) with a mean age of 73 ± 8 years and a mean dialysis duration of 4.6 ± 3.5 years. Of these, 87% of patients used assistive devices and 90% had care partners. We enrolled 12 care partners (75% women, 33% Black) with a mean age of 54 ± 16 years. From our patient and care partner interviews, we found three themes: (1) what care partners see, (2) what care partners do, and (3) what care partners feel. Regarding what they see, care partners witness a decline in patient mobility. Regarding what they do, care partners guide and facilitate activities and manage others who also assist. Regarding what they feel, care partners respect the patient's autonomy but experience frustration and worry about the patient's future mobility. Limitations: Modest sample size; single geographic area. Conclusions: In older adults receiving hemodialysis, care partners observe a decline in mobility and provide support for mobility. They respect the patient's autonomy but worry about future mobility losses. Future research should incorporate care partners in interventions that address mobility in older adults receiving hemodialysis.

Incidence and Durability of SARS-CoV-2 Antibodies in Patients with Cancer and Health Care Workers following the First Wave of the Pandemic.

BACKGROUND: Patients with cancer and health care workers (HCW) are at higher risk for SARS-CoV-2 infection. There are limited data regarding the rate of symptomatic versus asymptomatic infection and subsequent seropositivity in both populations. METHODS: We performed a prospective study of patients and HCW across two institutions during the first wave of the pandemic to analyze the prevalence of SARS-CoV-2 antibodies, the extent of associated symptoms, and durability of serologic response. RESULTS: In 1,953 persons (733 patients and 1,220 HCW), overall seropositivity rates for 3.1% patients (95% CI 2.0-4.7) and 3.7% HCW (95% CI 2.7-4.9, p=0.520), were similar. Each institutions' seropositivity rates were numerically higher in HCW than patients. Non-Hispanic Whites and Asians had lower antibody rates (2.8%, 95% CI 2.0-3.8 and 3.3%, 95% CI 1.2-7.0) compared to Hispanics (6.9%, 95% CI 3.4-12.4) and non-Hispanic Blacks (5.9%, 95% CI 3.3-9.7), p < 0.001. Among persons with a positive SARS-CoV-2 antibody, 87% of patients and 56% of HCW did not recall having had a fever. Among HCW, administrative and technical personnel were most likely to be seropositive. The rate of persistent seropositivity at 3 months was similar between patients and HCW and was not influenced by the reporting of fever, cancer type, or therapy. CONCLUSION: These data suggest that patients are not at higher risk for febrile SARS-CoV-2 infections or more transient immunity than HCWs. Furthermore, racial differences and lack of association with the extent of HCW contact with COVID-19 patients suggest that community rather than hospital virus exposure was a source of many infections.

Microarray assessment of methylation in individual mouse blastocyst stage embryos shows that in vitro culture may have widespread genomic effects.

BACKGROUND: Although assisted reproductive technology (ART) is reported to result in abnormal genomic imprinting and/or altered genomic methylation, few if any studies have used high-throughput methods to analyze genomic methylation in ART embryos. We hypothesized that a microarray-based assessment of genomic methylation could be used to reveal differences between ART and normal preimplantation embryos. METHODS: In this pilot study, we performed methylation-sensitive amplification of genomic DNA from preimplantation mouse blastocysts, obtained by natural mating and either maintained in vivo until E3.5 (n = 4) or cultured in vitro (n = 4) from E0.5 until E3.5. An oligonucleotide microarray was then used to perform comparative hybridization of amplified DNA, allowing us to assess relative methylation at ~16,000 loci on mouse chromosome 7. RESULTS: We show that for in vivo derived embryos, the methylation/microarray results were strikingly consistent. In contrast, all four in vitro cultured embryos showed evidence of generalized hypermethylation as well as greater locus-to-locus variability, when compared with in vivo derived embryos. Genomic segments that overlapped exons and CpG islands were most likely to be hypomethylated in both normal and experimental blastocysts. Other sequence features, such as repetitive elements, were not associated with the presence of or the degree of methylation. CONCLUSIONS: We conclude that a general assessment of genomic methylation in blastocyst stage embryos is technically feasible. Data from this small sample suggest that in vitro embryo culture is associated with generalized hypermethylation as well as increased locus-to-locus variability in methylation. However, it is premature to conclude that this is a general property of in vitro cultured blastocysts.

Development and validation of a prognostic 40-day mortality risk model among hospitalized patients with COVID-19.

OBJECTIVES: The development of a prognostic mortality risk model for hospitalized COVID-19 patients may facilitate patient treatment planning, comparisons of therapeutic strategies, and public health preparations. METHODS: We retrospectively reviewed the electronic health records of patients hospitalized within a 13-hospital New Jersey USA network between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2, with follow-up through May 29, 2020. With death or hospital discharge by day 40 as the primary endpoint, we used univariate followed by stepwise multivariate proportional hazard models to develop a risk score on one-half the data set, validated on the remainder, and converted the risk score into a patient-level predictive probability of 40-day mortality based on the combined dataset. RESULTS: The study population consisted of 3123 hospitalized COVID-19 patients; median age 63 years; 60% were men; 42% had >3 coexisting conditions. 713 (23%) patients died within 40 days of hospitalization for COVID-19. From 22 potential candidate factors 6 were found to be independent predictors of mortality and were included in the risk score model: age, respiratory rate ≥25/minute upon hospital presentation, oxygenation <94% on hospital presentation, and pre-hospital comorbidities of hypertension, coronary artery disease, or chronic renal disease. The risk score was highly prognostic of mortality in a training set and confirmatory set yielding in the combined dataset a hazard ratio of 1.80 (95% CI, 1.72, 1.87) for one unit increases. Using observed mortality within 20 equally sized bins of risk scores, a predictive model for an individual's 40-day risk of mortality was generated as -14.258 + 13.460*RS + 1.585*(RS-2.524)^2-0.403*(RS-2.524)^3. An online calculator of this 40-day COVID-19 mortality risk score is available at www.HackensackMeridianHealth.org/CovidRS. CONCLUSIONS: A risk score using six variables is able to prognosticate mortality within 40-days of hospitalization for COVID-19. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT04347993.

Bypass of hexavalent chromium-induced growth arrest by a protein tyrosine phosphatase inhibitor: enhanced survival and mutagenesis.

Although the consequences of genotoxic injury include cell cycle arrest and apoptosis, cell survival responses after genotoxic injury can produce intrinsic death-resistance and contribute to the development of a transformed phenotype. Protein tyrosine phosphatases (PTPs) are integral components of key survival pathways, and are responsible for their inactivation, while PTP inhibition is often associated with enhanced cell proliferation. Our aim was to elucidate signaling events that modulate cell survival after genotoxin exposure. Diploid human lung fibroblasts (HLF) were treated with Cr(VI) (as Na(2)CrO(4)), the soluble oxyanionic dissolution product of certain particulate chromates, which are well-documented human respiratory carcinogens. In vitro soluble Cr(VI) induces a wide spectrum of DNA damage, in both the presence and absence of a broad-range PTP inhibitor, sodium orthovanadate (SOV). Notably, SOV abrogated Cr(VI)-induced clonogenic lethality. The enhanced survival of Cr(VI)-exposed cells after SOV treatment was predominantly due to a bypass of cell cycle arrest, as there was no effect of the PTP inhibitor on Cr-induced apoptosis. Moreover, the SOV effect was not due to decreased Cr uptake as evidenced by unchanged Cr-DNA adduct burden. Additionally, the bypass of Cr-induced growth arrest by SOV was accompanied by a decrease in Cr(VI)-induced expression of cell cycle inhibiting genes, and an increase in Cr(VI)-induced expression of cell cycle promoting genes. Importantly, SOV resulted in an increase in forward mutations at the HPRT locus, supporting the hypothesis that PTP inhibition in the presence of certain types of DNA damage may lead to increased genomic instability, via bypass of cell cycle checkpoints.

Scoping Review: Physical Activity and Social Functioning in Young People With Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) affects ~1 in 59 people in North America and diagnoses continue to rise (Center for Disease Control and Prevention, 2018). Unfortunately, the exact cause of ASD is unknown and therapy remains the primary means of intervention. People with ASD experience social and behavioral deficits associated with the disorder, which affect all aspects of life such as academics, relationships, and physical activity. Research has shown a relationship between physical activity and social skills in typically developing individuals; however, this relationship is less understood in people with ASD. The purpose of this scoping review was to uncover what is known about ASD, physical activity, and social functioning. The authors searched four databases and included 40 primary research articles in the review, most of which demonstrated a relationship between physical activity and social functioning for people with ASD. The relationship appears bidirectional: social functioning influences physical activity (to a lesser extent) and physical activity influences social functioning (to a greater extent). Regrettably, there were many limitations in these articles, such as small sample sizes and the under-representation of females and adults. Therefore, the review highlights several directions for future research.

Formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA): a critical review of the research.

PURPOSE: To summarize results of randomized controlled trials (RCTs) evaluating growth, cognitive, neurological, and visual development of term infants supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA). DESIGN AND METHODS: The Boyack and Lookinland Methodological Quality Index (MQI) was used to evaluate data from RCTs identified from multiple data bases. RESULTS: Six of ten studies found the addition of DHA and ARA to have no significant effect on infant development. PRACTICE IMPLICATIONS: More expensive formula with endogenous DHA and ARA is not necessary. Results from longer studies currently underway will be beneficial.

Evaluation of extended and continuous use oral contraceptives.

Oral contraceptives are classically given in a cyclic manner with 21 days of active pills followed by 7 days of placebo. In the past 4 years, new oral contraceptives have been introduced which either shorten the placebo time, lengthen the active pills (extended cycle), or provide active pills every day (continuous). These concepts are not new; extended and continuous pills were first studied in the 1960s and 1970s and have been provided in an off-label manner by gynecologists to treat menstrual disorders, such as menorrhagia and dysmenorrhea, and gynecologic disorders, such as endometriosis. Now that extended and continuous combined oral contraceptives are available for all patients, it is critical for providers to understand the physiology, dosing, side effects, and benefits of this form of oral contraceptive. This article reviews the history and the potential uses of the new continuous combined oral contraceptive.

Use of phenazopyridine for reducing discomfort during embryo transfer.

OBJECTIVE: The embryo transfer is a critical part of in vitro fertilization. When performed under abdominal ultrasound guidance, the embryo transfer procedure requires a full bladder. Patients often state that the discomfort of the distended bladder causes more pain than the actual transfer procedure. Phenazopyridine HCl is a bladder analgesic. The objective of this study was to determine if a single dose of phenazopyridine prior to embryo transfer reduces patient discomfort during that procedure. DESIGN: Prospective randomized double-blinded clinical trial. SETTING: University-based Reproductive Medicine practice. PATIENT(S): Eighty-five reproductive age infertile women undergoing in vitro fertilization. INTERVENTION(S): Phenazopyridine (200 mg) or placebo taken 1 hour prior to embryo transfer utilizing transabdominal sonography. MAIN OUTCOME MEASURE(S): Pain as assessed by visual analogue pain scale and physician and nurse assessment of patient discomfort. RESULT(S): Study groups were similar in their demographic background. Mean pain score as assessed by a visual analogue pain scale during the procedure was 2.95 +/- 2.4 in the placebo group, and 3.03 +/- 2.6 in the active medication group (NS). There were also no significant differences in the observations of pain assessments. CONCLUSION(S): Phenazopyridine used in a single dose prior to embryo transfer does not alleviate patient discomfort.

Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer.

The objective of this study was to compare the implantation rate, pregnancy rate and endometrial thickness of frozen-thawed embryo transfers using endometrial preparation with either an artificial cycle or stimulated cycle. This was a prospective randomized trial at a single academic IVF centre. Seventy-seven patients undergoing artificial cycles received oral oestradiol; patients with endometrium < 7 mm on day 9-10 were switched to vaginal oestradiol. Eighty-six patients undergoing stimulated cycles received recombinant FSH followed by human gonadotrophin hormone injection. Vaginal progesterone was begun 2 or 3 days prior to embryo transfer. There was no difference in implantation rate (8.5% versus 7.3%), pregnancy rate (16% versus 13%), cancellation rate (both 23%) or endometrium thickness (8.7 +/- 1.1 mm versus 8.7 +/- 1.0 mm) between artificial and stimulated cycles. Stimulated cycles had a higher incidence of thin endometrium (27% versus 5%, P < 0.01). In artificial cycles, patients switched to vaginal oestradiol had improved pregnancy rate (31%) versus patients who received oral oestradiol alone (13%) (P = 0.05). It is concluded that artificial and stimulated cycles produce comparable pregnancy rates, implantation rates, cancellation rates and endometrial thickness, although stimulated cycles have a higher incidence of thin endometrium. Vaginal oestradiol supplementation improved implantation rates.