bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial–Ethnic and Socioeconomic Disparities in Guideline-Adherent Treatment for Endometrial Cancer
Authors: Rodriguez Victoria E. , LeBrón Alana M. W. , Chang Jenny , Bristow Robert E.
Published: June 2021

OBJECTIVE:

To evaluate the association of race–ethnicity and neighborhood socioeconomic status with adherence to National Comprehensive Cancer Network guidelines for endometrial carcinoma.

METHODS:

Data are from the SEER (Surveillance, Epidemiology, and End Results) cancer registry of women diagnosed with endometrial carcinoma for the years 2006–2015. The sample included 83,883 women after inclusion and exclusion criteria were applied. Descriptive statistics, bivariate analyses, univariate, and multivariate logistic regression models were performed to evaluate the association between race–ethnicity and neighborhood socioeconomic status with adherence to treatment guidelines.

RESULTS:

After controlling for demographic and clinical covariates, Black (odds ratio [OR] 0.89, P<.001), Latina (OR .92, P<.001), and American Indian or Alaska Native (OR 0.82, P=.034) women had lower odds of receiving adherent treatment and Asian (OR 1.14, P<.001) and Native Hawaiian or Pacific Islander (OR 1.19 P=.012) women had higher odds of receiving adherent treatment compared with White women. After controlling for covariates, there was a gradient by neighborhood socioeconomic status: women in the high–middle (OR 0.89, P<.001), middle (OR 0.84, P<.001), low–middle (OR 0.80, P<.001), and lowest (OR 0.73, P<.001) neighborhood socioeconomic status categories had lower odds of receiving adherent treatment than the those in the highest neighborhood socioeconomic status group.

CONCLUSIONS:

Findings from this study suggest there are racial–ethnic and neighborhood socioeconomic disparities in National Comprehensive Cancer Network treatment adherence for endometrial cancer. Standard treatment therapies should not differ based on sociodemographics. Interventions are needed to ensure that equitable cancer treatment practices are available for all individuals, regardless of racial–ethnic or socioeconomic background.
Considerations and Recommendations for Pregnancy and Postpartum Care for People Living With Human Immunodeficiency Virus
Authors: Givens Matthew , Levison Judy , Rahangdale Lisa
Published: June 2021

Considerable strides have been made in reducing the rate of perinatal human immunodeficiency virus (HIV) transmission within the United States and around the globe. Despite this progress, preventable perinatal HIV transmission continues to occur. Adherence to HIV screening and treatment recommendations preconception and during pregnancy can greatly reduce the risk of perinatal HIV transmission. Early and consistent usage of highly active antiretroviral therapy (ART) can greatly lower the HIV viral load, thus minimizing HIV transmission risk. Additional intrapartum interventions can further reduce the risk of HIV transmission. Although the current standard is to recommend abstinence from breastfeeding for individuals living with HIV in settings where there is safe access to breast milk alternatives (such as in the United States), there is guidance available on counseling and risk-reduction strategies for individuals on ART with an undetectable viral load who elect to breastfeed.
Physical Restraints in Critically Ill Children: A Multicenter Longitudinal Point Prevalence Study*
Authors: Ikebe Ryo , Kawaguchi Atsushi , Kawasaki Tatsuya , Miura Norimasa , Matsuishi Yujiro , Takeuchi Muneyuki , Nittsu Takehiro , Fujiwara Naoki , Shimoyama Shinya , Nakayama Yuko , Akita Chisato , Munekawa Ikkei , Kajinishi Yumi , Sasaki Emi , Sakamoto Katsuko , Matsuoka Wakato
Published: June 2021

OBJECTIVES:

We elucidate to investigate the prevalence of and factors associated with the use of physical restraints among critically ill or injured children in PICUs.

DESIGN:

This was a multicenter, longitudinal point prevalence study.

SETTING:

We included 26 PICUs in Japan.

PATIENTS:

Included children were 1 month to 10 years old. We screened all admitted patients in the PICUs on three study dates (in March, June, and September 2019).

INTERVENTION:

None.

MEASUREMENTS AND MAIN RESULTS:

We collected prevalence and demographic characteristics of critically ill or injured children with physical restraints, as well as details of physical restraints, including indications and treatments provided. A total of 398 children were screened in the participating PICUs on the three data collection dates. The prevalence of children with physical restraints was 53% (211/398). Wrist restraint bands were the most frequently used means (55%, 117/211) for potential contingent events. The adjusted odds of using physical restraint in patients 1–2 years old was 2.3 (95% CI, 1.3–4.0) compared with children less than 1 year old. When looking at the individual hospital effect, units without a prespecified practice policy for physical restraints management or those with more than 10 beds were more likely to use physical restraints.

CONCLUSIONS:

The prevalence of physical restraints in critically ill or injured children was high, and significant variation was observed among PICUs. Our study findings suggested that patient age, unit size, and practice policy of physical restraint could be associated with more frequent use of physical restraints.
Epidemiology, Outcomes, and Trends of Patients With Sepsis and Opioid-Related Hospitalizations in U.S. Hospitals*
Authors: Alrawashdeh Mohammad , Klompas Michael , Kimmel Simeon , Larochelle Marc R. , Gokhale Runa H. , Dantes Raymund B. , Hoots Brooke , Hatfield Kelly M. , Reddy Sujan C. , Fiore Anthony E. , Septimus Edward J. , Kadri Sameer S. , Poland Russell , Sands Kenneth , Rhee Chanu
Published: June 2021

OBJECTIVES:

Widespread use and misuse of prescription and illicit opioids have exposed millions to health risks including serious infectious complications. Little is known, however, about the association between opioid use and sepsis.

DESIGN:

Retrospective cohort study.

SETTING:

About 373 U.S. hospitals.

Patients:

Adults hospitalized between January 2009 and September 2015.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Sepsis was identified by clinical indicators of concurrent infection and organ dysfunction. Opioid-related hospitalizations were identified by the International Classification of Diseases, 9th Revision, Clinical Modification codes and/or inpatient orders for buprenorphine. Clinical characteristics and outcomes were compared by sepsis and opioid-related hospitalization status. The association between opioid-related hospitalization and all-cause, in-hospital mortality in patients with sepsis was assessed using mixed-effects logistic models to adjust for baseline characteristics and severity of illness.

The cohort included 6,715,286 hospitalizations; 375,479 (5.6%) had sepsis, 130,399 (1.9%) had opioid-related hospitalizations, and 8,764 (0.1%) had both. Compared with sepsis patients without opioid-related hospitalizations (n = 366,715), sepsis patients with opioid-related hospitalizations (n = 8,764) were younger (mean 52.3 vs 66.9 yr) and healthier (mean Elixhauser score 5.4 vs 10.5), had more bloodstream infections from Gram-positive and fungal pathogens (68.9% vs 47.0% and 10.6% vs 6.4%, respectively), and had lower in-hospital mortality rates (10.6% vs 16.2%; adjusted odds ratio, 0.73; 95% CI, 0.60–0.79; p < 0.001 for all comparisons). Of 1,803 patients with opioid-related hospitalizations who died in-hospital, 928 (51.5%) had sepsis. Opioid-related hospitalizations accounted for 1.5% of all sepsis-associated deaths, including 5.7% of sepsis deaths among patients less than 50 years old. From 2009 to 2015, the proportion of sepsis hospitalizations that were opioid-related increased by 77% (95% CI, 40.7–123.5%).

CONCLUSIONS:

Sepsis is an important cause of morbidity and mortality in patients with opioid-related hospitalizations, and opioid-related hospitalizations contribute disproportionately to sepsis-associated deaths among younger patients. In addition to ongoing efforts to combat the opioid crisis, public health agencies should focus on raising awareness about sepsis among patients who use opioids and their providers.
Pathophysiologic Signature of Impending ICU Hypoglycemia in Bedside Monitoring and Electronic Health Record Data: Model Development and External Validation
Authors: Horton William B. , Barros Andrew J. , Andris Robert T. , Clark Matthew T. , Moorman J. Randall
Published: June 2021

OBJECTIVES:

We tested the hypothesis that routine monitoring data could describe a detailed and distinct pathophysiologic phenotype of impending hypoglycemia in adult ICU patients.

DESIGN:

Retrospective analysis leading to model development and validation.

SETTING:

All ICU admissions wherein patients received insulin therapy during a 4-year period at the University of Virginia Medical Center. Each ICU was equipped with continuous physiologic monitoring systems whose signals were archived in an electronic data warehouse along with the entire medical record.

PATIENTS:

Eleven thousand eight hundred forty-seven ICU patient admissions.

INTERVENTIONS:

The primary outcome was hypoglycemia, defined as any episode of blood glucose less than 70 mg/dL where 50% dextrose injection was administered within 1 hour. We used 61 physiologic markers (including vital signs, laboratory values, demographics, and continuous cardiorespiratory monitoring variables) to inform the model.

MEASUREMENTS AND MAIN RESULTS:

Our dataset consisted of 11,847 ICU patient admissions, 721 (6.1%) of which had one or more hypoglycemic episodes. Multivariable logistic regression analysis revealed a pathophysiologic signature of 41 independent variables that best characterized ICU hypoglycemia. The final model had a cross-validated area under the receiver operating characteristic curve of 0.83 (95% CI, 0.78–0.87) for prediction of impending ICU hypoglycemia. We externally validated the model in the Medical Information Mart for Intensive Care III critical care dataset, where it also demonstrated good performance with an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.77–0.81).

CONCLUSIONS:

We used data from a large number of critically ill inpatients to develop and externally validate a predictive model of impending ICU hypoglycemia. Future steps include incorporating this model into a clinical decision support system and testing its effects in a multicenter randomized controlled clinical trial.
Association Between an Increase in Serum Sodium and In-Hospital Mortality in Critically Ill Patients*
Authors: Grim Chloe C. A. , Termorshuizen Fabian , Bosman Robert J. , Cremer Olaf L. , Meinders Arend Jan , Nijsten Maarten W. N. , Pickkers Peter , de Man Angelique M. E. , Schultz Marcus J. , van Vliet Peter , Weigel Joachim D. , Helmerhorst Hendrik J. F. , de Keizer Nicolette F. , de Jonge Evert
Published: June 2021

OBJECTIVES:

In critically ill patients, dysnatremia is common, and in these patients, in-hospital mortality is higher. It remains unknown whether changes of serum sodium after ICU admission affect mortality, especially whether normalization of mild hyponatremia improves survival.

DESIGN:

Retrospective cohort study.

SETTING:

Ten Dutch ICUs between January 2011 and April 2017.

Patients:

Adult patients were included if at least one serum sodium measurement within 24 hours of ICU admission and at least one serum sodium measurement 24–48 hours after ICU admission were available.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A logistic regression model adjusted for age, sex, and Acute Physiology and Chronic Health Evaluation-IV–predicted mortality was used to assess the difference between mean of sodium measurements 24–48 hours after ICU admission and first serum sodium measurement at ICU admission (Δ48 hr-[Na]) and in-hospital mortality. In total, 36,660 patients were included for analysis. An increase in serum sodium was independently associated with a higher risk of in-hospital mortality in patients admitted with normonatremia (Δ48 hr-[Na] 5–10 mmol/L odds ratio: 1.61 [1.44–1.79], Δ48 hr-[Na] > 10 mmol/L odds ratio: 4.10 [3.20–5.24]) and hypernatremia (Δ48 hr-[Na] 5–10 mmol/L odds ratio: 1.47 [1.02–2.14], Δ48 hr-[Na] > 10 mmol/L odds ratio: 8.46 [3.31–21.64]). In patients admitted with mild hyponatremia and Δ48 hr-[Na] greater than 5 mmol/L, no significant difference in hospital mortality was found (odds ratio, 1.11 [0.99–1.25]).

CONCLUSIONS:

An increase in serum sodium in the first 48 hours of ICU admission was associated with higher in-hospital mortality in patients admitted with normonatremia and in patients admitted with hypernatremia.
Age at Primary Cleft Lip Repair: A Potential Bellwether Indicator for Pediatric Surgery
Authors: Vanderburg Richard , Alonso Nivaldo , Desai Priya , Donkor Peter , Mossey Peter , Stieber Erin , V. Mehendale Felicity
Published: June 2021

Background:

The bellwether procedures described by the Lancet Commission on Global Surgery represent the ability to deliver adult surgical services after there is a clear and easily made diagnosis. There is a need for pediatric surgery bellwether indicators. A pediatric bellwether indicator would ideally be a routinely performed procedure, for a relatively common condition that, in itself, is rarely lethal at birth, but that should ideally be treated with surgery by a standard age. Additionally, the condition should be easy to diagnose, to minimize the confounding effects of delays or failures in diagnosis. In this study, we propose the age at primary cleft lip (CL) repair as a bellwether indicator for pediatric surgery.

Method:

We reviewed the surgical records of 71,346 primary cleft surgery patients and ultimately studied age at CL repair in 40,179 patients from 73 countries, treated by Smile Train partners for 2019. Data from Smile Train’s database were correlated with World Bank and WHO indicators.

Results:

Countries with a higher average age at CL repair (delayed access to surgery) had higher maternal, infant, and child mortality rates as well as a greater risk of catastrophic health expenditure for surgery. There was also a negative correlation between delayed CL repair and specialist surgical workforce numbers, life expectancy, percentage of deliveries by C-section, total health expenditure per capita, and Lancet Commission on Global Surgery procedure rates.

Conclusion:

These findings suggest that age at CL repair has potential to serve as a bellwether indicator for pediatric surgical capacity in Lower- and Middle-income Countries.
Meditation and Mindfulness in Pregnancy and Postpartum: A Review of the Evidence
Authors: Babbar Shilpa , Oyarzabal Alejandro J. , Oyarzabal Esteban A.
Published: June 2021

Given their growing popularity, mindfulness practices including meditation are actively being studied in clinical trials to assess their efficacy at improving health outcomes during pregnancy and the postpartum period. We conducted a literature review to compile these studies and assessed their findings. There is sufficient evidence to support the practice of mindfulness practices in pregnancy to reduce anxiety, depression, and stress during pregnancy, which may continue to have beneficial effects through the postpartum period. There is limited evidence on the benefits of mindfulness and meditation for other aspects of pregnancy. However, due to the low-risk nature of these techniques, all women should be encouraged to engage in mindfulness practices during pregnancy.
Prevalence and Antimicrobial Resistance of Bacteria in Children With Acute Otitis Media and Ear Discharge
Authors: Hullegie Saskia , Venekamp Roderick P. , van Dongen Thijs M. A. , Hay Alastair D. , Moore Michael V. , Little Paul , Schilder Anne G. M. , Damoiseaux Roger A. M. J.
Published: June 2021

Background:

Of children with acute otitis media (AOM), 15%–20% present with acute onset ear discharge due to a spontaneous perforation of the tympanic membrane (AOMd). This review aims to quantify the prevalence and antimicrobial resistance (AMR) status of bacteria in children with AOMd in the pneumococcal conjugate vaccine (PCV) era.

Methods:

Systematic searches were performed in PubMed, EMBASE and Cochrane Library from inception to June 7, 2019. Two reviewers extracted relevant data and assessed risk of bias independently. All English studies reporting any prevalence and/or AMR data of bacterial middle ear isolates from children with AOMd were included. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal checklist.

Results:

Of 4088 unique records retrieved, 19 studies (10,560 children) were included. Overall quality was judged good. Streptococcus pneumoniae (median 26.1%, range 9.1%–47.9%), Haemophilus influenzae (median 18.8%, range 3.9%–55.3%), Staphylococcus aureus (median 12.3%, range 2.3%–34.9%) and Streptococcus pyogenes (median 11.8%, range 1.0%–30.9%) were the most prevalent bacteria. In 76.0% (median, range 48.7%–100.0%, 19 studies, 1,429 children) any bacterium was identified. AMR data were sparse and mainly limited to S. pneumoniae. We found no evidence of a clear shift in the prevalence of bacteria and AMR over time.

Conclusions:

In children with AOMd, S. pneumoniae and H. influenzae are the 2 predominant bacteria, followed by S. aureus and S. pyogenes in the post-PCV era. AMR data are sparse and no clearly change over time was observed. Ongoing surveillance of the microbiology profile in children with AOMd is warranted to guide antibiotic selection and to assess the impact of children’s PCV status.
Use of the Whole Country Insulin Consumption Data in Israel to Determine the Prevalence of Type 1 Diabetes in Children <5 Years of Age Before and During Rotavirus Vaccination
Authors: Blumenfeld Orit , Lawrence Gabriella , Shulman Lester M. , Laron Zvi
Published: June 2021

Background:

Recent studies showed that rotavirus vaccination may affect the prevalence of type 1 diabetes (T1D). The aim of the study was to determine the prevalence of early childhood (<5 years) T1D before and during the introduction of rotavirus vaccination in Israel by syndromic surveillance.

Methods:

Data on insulin purchases reported by Israel’s four Health Maintenance Organizations (HMOs) were retrieved from the National Program for Quality Indicators in Community Healthcare.

Results:

During the prevaccination years (2002–2007), a steady increase in insulin purchases was reported in the young (<5 years). The period percent change (PC) of children <5 years old diagnosed with T1D inferred from purchased insulin prescriptions increased by 50.0%, and the annual percent change (APC) increased by 10.0% (p = 0.01). During the period of free, universal Rotavirus vaccination (2011–2018), the PC for T1D diagnoses among children <5 years of age decreased by 3.8% with an APC of −2.5% (p = 0.14). There was a significant difference (p = 0.002) between the increasing trend in insulin use before vaccination versus the decreasing trend after vaccination.

Conclusion:

Rotavirus vaccination correlated with attenuation of the increasing rate in the prevalence of T1D in <5-year-old children in Israel.
Establishing Benchmarks for Antimicrobial Use in Canadian Children’s Hospitals
Authors: Blackburn Julie , Barrowman Nicholas , Bowes Jennifer , Tsampalieros Anne , Le Saux Nicole
Published: June 2021

Background:

Point prevalence surveys (PPS) are potentially useful to measure antimicrobial use across institutions. The objectives of the study were to describe and compare antimicrobial use between pediatric hospitals in Canada.

Methods:

Fifteen pediatric hospitals all with pediatric infectious diseases service participated in 2 single-day PPS in 2018/19. Children <18 years of age who were inpatients were included. Age, service, clinical diagnosis as well as name, route, and start date for each antimicrobial was collected. Antibiotics were grouped according to the World Health Organization AWaRe classification.

Results:

There were 3924 inpatient patients-days representing 2729 children and 1195 infants in neonatal intensive care units (NICU) surveyed. Among non-NICU patients, 1210 (44.3%) received 1830 antimicrobials of which 73.9% were for empiric or pathogen-directed therapy and 25.6% for prophylaxis. The mean proportion of core Access and Watch group antibiotics was 45.8% and 63.5%, respectively, with no differences in means between tertiary and quaternary care sites. Among 1195 infants in NICU, 19.7% received 410 antimicrobials of which 17.1% were for prophylaxis and a mean of 45.4% were Watch group antibiotics. Of patients admitted for community-acquired pneumonia, 32.7% received penicillin or aminopenicillins only with variability among sites.

Conclusions:

PPS of antimicrobial use in Canadian pediatric hospitals revealed a high proportion of Watch group (broader spectrum) antibiotics, even among children with community-acquired pneumonia. This study demonstrates the feasibility of PPS to document antimicrobial use and potentially to use this data to establish goals for decreasing both overall and Watch group antibiotics.
Prescribing Tamoxifen in Patients With Mood Disorders
Authors: Carmassi Claudia , Cordone Annalisa , Dell'Oste Valerio , Pedrinelli Virginia , Pardini Francesco , Simoncini Marly , Dell'Osso Liliana
Published: June 2021

Purpose/Background

Tamoxifen is a selective estrogen receptor modulator widely used for treatment and prevention of estrogenic receptor–positive breast cancer. Tamoxifen is an object of growing interest in psychopharmacology as an antimanic drug, because it inhibits the protein kinase C, a molecular target of bipolar disorder. Consistently, the potential depressive effect of tamoxifen has been repeatedly reported.

Methods/Procedures

This article systematically reviews studies examining tamoxifen impact on mood, exploring either its potential therapeutic use as antimanic agent or its potential depressive effect.

Findings

Eight studies explored tamoxifen antimanic properties, all, but one, reported a rapid and efficacious antimanic action. As to the depressive effect, 9 cohort studies emerged among which 4 pointed out an increased risk of depression. Seven case reports described the onset or exacerbation of depressive episodes besides 1 case series study reported a high rate of depressive symptoms. In addition, 1 case report study described a tamoxifen-induced manic episode.

Implications/Conclusions

The present review highlights tamoxifen treatment as a possible trigger of mood symptoms onset or exacerbation in vulnerable patients. Accordingly, patients with a history of mood disorders may require a close clinical surveillance during tamoxifen use. At the same time, the use of tamoxifen as an antimanic agent in psychiatric settings requires caution, as available evidence came from small-sample studies with short observation time. More studies are needed to define how long-term tamoxifen use may affect the course of bipolar disorder.
Interpretation and Application of the Likelihood Ratio to Clinical Practice in Thoracic Oncology
Authors: Ost David E.
Published: June 2021

Likelihood ratios (LRs) are a method to evaluate diagnostic test performance and assist in clinical decision making. While sensitivity and specificity are useful for binary tests, they cannot be directly applied to tests with >2 possible test results. LRs can be used for diagnostic tests with 2 or more possible test results and are also suitable for tests with continuous results. In this paper we review the concepts of LRs and how they relate to sensitivity and specificity. Practical examples from the pulmonary literature of how LRs are used to calculate posttest disease probabilities using Bayes’ theorem are provided. These include examples when there are 3 or more categorical test results that have distinct interpretations (eg, cytology results from endobronchial ultrasound) as well as continuous test results (eg, computed tomography lymph node size and probability of metastasis). We also highlight some problems, pitfalls, and misunderstandings about LRs in clinical practice. We use the example of how the Nodify XL2 test incorrectly calculates and applies LRs, which may lead to falsely low estimates of the probability of cancer in some pulmonary nodules.
Neonatal Nurses' Perceptions of Palliative Care in the Neonatal Intensive Care Unit
Authors: Chin Susan Di Nonno , Paraszczuk Ann Marie , Eckardt Patricia , Bressler Toby
Published: June 2021

Purpose:

Neonatal palliative care is widely endorsed as an essential aspect of neonatal intensive care unit (NICU) practice, yet inconsistencies in its use continue to exist. We examined neonatal nurses' perceptions of barriers and facilitators to palliative care in their NICU setting.

Study Design and Methods:

A cross-sectional design using the Neonatal Palliative Care Attitude Scale (NiPCAS™©) was administered using an online survey distributed to neonatal nurses through the Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) and National Association of Neonatal Nurses (NANN). Parametric statistical analyses were conducted to explore relationships between unit policy and neonatal palliative care (NPC) education, and the nurses' perceptions.

Results:

Ninety-nine of 1,800 AWHONN members who identified as NICU nurses completed the survey, representing a response rate of 5.5% and 101 of 4,000 NANN members who subscribe to the MYNANN message boards completed the survey, reflecting a 2.5% response rate. N = 200 surveys were completed with minimal data missing, resulting in a final sample of 200. Exploratory factor analysis yielded these subconstructs: Unit Culture, Resources, and Perceived Inappropriate Care. Barriers identified were Perceived Inappropriate Care and Societal Understanding of NPC. A positive correlation was noted for NiPCAS™© scores and unit culture support (r(185) = .66, n = 187, p < .01), unit NPC policy (r(184) = .446, n = 186, p < .01), and NPC education (r(185) = .373, n = 187, p < .01).

Clinical Implications:

Nurses who work in a NICU with an NPC policy and who have received palliative care education demonstrated more favorable attitudes toward NPC. Policy and educational programs are important strategies to promote high-quality care for high-risk infants and their families.
Relationship Between Infant Tongue-Tie and Maternal Wellbeing
Authors: Hill Rebecca R. , Wong John , Parikh Gayatri S.
Published: June 2021

Background:

Tongue-tie is a mild oral anomaly that can cause feeding challenges, especially for breastfeeding mothers and infants. Delayed diagnosis may place mothers at increased risk of stress and impaired mother–infant bonding when feeding does not go as planned. The purpose of this study was to explore the risk for altered maternal wellbeing (e.g., stress and maternal–infant bonding) in mothers of infants with tongue-tie-using-a mixed-methods, cross-sectional study.

Methods:

We recruited mothers from two sites to participate in a survey about their experiences with tongue-tie: Facebook™ tongue-tie support group and a local pediatric dental office where frenotomy is commonly performed. Inclusion criteria were mothers 18 or older; able to read, write, and understand English. Infants were under the age of 1 year when diagnosed with tongue-tie. The survey contained both selection and open-text entry questions. Maternal–infant bonding was assessed using the Postpartum Bonding Questionnaire and maternal stress was measured using the Parental Stress Scale.

Results:

N = 113 mothers participated. Findings suggest that mothers of infants with tongue-tie report increased stress, especially when a diagnosis of tongue-tie is delayed. After correction, maternal wellbeing, the breastfeeding relationship, and maternal report of infant temperament improved.

Clinical Implications:

Early assessment, diagnosis, and management of tongue-tie are important. Partner support is helpful in fostering the mother–infant relationship. Future research is needed to understand barriers to appropriate referrals and delay in treatment of tongue-tie.
Cotinine Fluctuation in Maternal Saliva During and After Pregnancy
Authors: Gwon Seok Hyun , Jeong Suyong , Bullock Linda
Published: June 2021

Purpose:

The purpose of this study was to determine maternal cotinine levels in saliva at the first (T-1) and third trimesters of pregnancy (T-2), and postpartum (T-3) among women who reported smoking a consistent number of cigarettes. The goal was to generate data to provide suggestions about how nurses can improve patient outcomes for women who smoke.

Methods:

Saliva cotinine values obtained from the randomized controlled trial (BabyBEEP) were used for this secondary analysis. We examined variations in saliva cotinine between the first and third trimesters of pregnancy and postpartum among light and heavy smokers. Cotinine values for pregnant smokers who were in the control group (not randomized to any intervention) and reported smoking the same range of cigarettes during and after pregnancy were used for the analyses (n = 43). Descriptive statistics and repeated-measures ANOVA were used for analyses.

Results:

There were differences in maternal saliva cotinine levels across the different time points and between the groups. There was a significant interaction effect between time and group. Cotinine decreased from T-1 to T-2 in heavy smokers and increased from T-2 to T-3 among both light and heavy smokers. Cotinine at T-3 was higher than T-1 among light smokers.

Clinical Implications:

Findings support accelerated nicotine metabolism during pregnancy and need for smoking cessation efforts throughout pregnancy to help women stay smoke free during postpartum.
HIV General Population Surveys: Shedding Light on the Status of HIV Epidemics and Informing Future Actions
Authors: Porter Laura , Bello George , Nkambule Rejoice , Justman Jessica
Published: June 2021

Nationally representative household surveys of the general population can provide critical assessments of the status of HIV epidemics and the impact of national HIV programs. With lessons learned from earlier surveys, PEPFAR has supported HIV-focused surveys in high burden countries to measure known HIV status, access to HIV treatment, and viral suppression, and, by using novel HIV recency assays, to estimate HIV incidence. The results from the initial population-based HIV impact assessments have transformed global HIV programming, demonstrating unexpected progress in population viral suppression and the persistent burden of high HIV incidence among adolescent girls and young women. The findings highlight the importance of tailoring programs to engage men more effectively in HIV testing and treatment. The collection of manuscripts summarized in this overview of the Supplement describe the methods and selected key findings from the initial population-based HIV impact assessment surveys. Taken together, the efforts described in these manuscripts have advanced survey and laboratory capacity and guided HIV programs toward the goal of ending the global epidemic.
HIV-1 Recent Infection Testing Algorithm With Antiretroviral Drug Detection to Improve Accuracy of Incidence Estimates
Authors: Voetsch Andrew C. , Duong Yen T. , Stupp Paul , Saito Suzue , McCracken Stephen , Dobbs Trudy , Winterhalter Frieda S. , Williams Daniel B. , Mengistu Assegid , Mugurungi Owen , Chikwanda Prisca , Musuka Godfrey , Ndongmo Clement B. , Dlamini Sindisiwe , Nuwagaba-Biribonwoha Harriet , Pasipamire Munyaradzi , Tegbaru Belete , Eshetu Frehywot , Biraro Samuel , Ward Jennifer , Aibo Dorothy , Kabala Andrew , Mgomella George S. , Malewo Optatus , Mushi Jeremiah , Payne Danielle , Mengistu Yohannes , Asiimwe Fred , Shang Judith D. , Dokubo Emily K. , Eno Laura T. , Zoung-Kanyi Bissek Anne-Cécile , Kingwara Leonard , Junghae Muthoni , Kiiru John N. , Mwesigwa Richard C.N. , Balachandra Shirish , Lobognon Roger , Kampira Elizabeth , Detorio Mervi , Yufenyuy Ernest L. , Brown Kristin , Patel Hetal K. , Parekh Bharat S.
Published: June 2021

Background:

HIV-1 incidence calculation currently includes recency classification by HIV-1 incidence assay and unsuppressed viral load (VL ≥ 1000 copies/mL) in a recent infection testing algorithm (RITA). However, persons with recent classification not virally suppressed and taking antiretroviral (ARV) medication may be misclassified.

Setting:

We used data from 13 African household surveys to describe the impact of an ARV-adjusted RITA on HIV-1 incidence estimates.

Methods:

HIV-seropositive samples were tested for recency using the HIV-1 Limiting Antigen (LAg)-Avidity enzyme immunoassay, HIV-1 viral load, ARVs used in each country, and ARV drug resistance. LAg-recent result was defined as normalized optical density values ≤1.5. We compared HIV-1 incidence estimates using 2 RITA: RITA1: LAg-recent + VL ≥ 1000 copies/mL and RITA2: RITA1 + undetectable ARV. We explored RITA2 with self-reported ARV use and with clinical history.

Results:

Overall, 357 adult HIV-positive participants were classified as having recent infection with RITA1. RITA2 reclassified 55 (15.4%) persons with detectable ARV as having long-term infection. Those with detectable ARV were significantly more likely to be aware of their HIV-positive status (84% vs. 10%) and had higher levels of drug resistance (74% vs. 26%) than those without detectable ARV. RITA2 incidence was lower than RITA1 incidence (range, 0%–30% decrease), resulting in decreased estimated new infections from 390,000 to 341,000 across the 13 countries. Incidence estimates were similar using detectable or self-reported ARV (R2 > 0.995).

Conclusions:

Including ARV in RITA2 improved the accuracy of HIV-1 incidence estimates by removing participants with likely long-term HIV infection.
Analysis of the Positional Relationship Among the Operator, Camera, and Monitor: Overcoming the Difficulties of Mirror-image Conditions During Laparoscopic Surgery
Authors: Inagaki Yuriko , Kawai Kazushige , Nishikawa Takeshi , Ishii Hiroaki , Emoto Shigenobu , Murono Koji , Kaneko Manabu , Sasaki Kazuhito , Nozawa Hiroaki , Ishihara Soichiro
Published: June 2021

Background:

Although methods to overcome difficulties associated with mirror-image conditions have been investigated, the ideal spatial relationship among the operator line of sight, monitor location, and camera location remains unclear. Moreover, the best training method for improving laparoscopic surgical skills under varying operator line of sight, camera, and monitor positions is unknown. We aimed to investigate the role of laparoscopic training under mirror-image conditions in improving surgical efficiency and whether prior surgical experience affects such training.

Methods:

This prospective study was conducted at the Department of Surgical Oncology, Tokyo University, Japan. Twenty-five surgeons participated. Novice (n=14), trained (n=7), and expert (n=4) participants performed the simulated task in a box trainer while varying the positional relationships among the surgeons, camera, and monitor. Five patterns were repeatedly performed 5 times per day for 4 days over 2 weeks.

Results:

The most significant differences in terms of the time required to complete the task under mirror-image conditions among the 3 groups were on day 1 (novices: 185.8 s, trained: 79.7 s, and experts: 46.5 s, P=0.009). However, after 4 days of training, the corresponding times did not differ among the 3 groups (26.0, 30.7, and 23.1 s, respectively; P=0.415). Laparoscopic training was sufficiently effective under mirror-image conditions.

Conclusions:

Mirror-image surgical conditions provided the most difficult setting, because surgeons and assistants often became disoriented, and task performance was most degraded. However, just 4 days of training was found to be sufficient to overcome the difficulties encountered while performing laparoscopic procedures under mirror-image conditions.
Blunt adrenal gland injury: The impact of extra-abdominal injury
Authors: Tanizaki Shinsuke , Maeda Shigenobu , Ishida Hiroshi
Published: June 2021

BACKGROUND

Blunt adrenal gland injuries are considered uncommon. Moreover, the factors associated with the mechanisms of the injury following blunt trauma are unclear. In this study, we determined the factors associated with blunt adrenal gland injury (BAGI).

MATERIALS AND METHODS

A total of 315 patients with blunt abdominal trauma were admitted to our institution during a 12-year period. After excluding 26 patients who were under 18 years old and 27 patients who were in cardiopulmonary arrest on arrival, 262 eligible patients were retrospectively reviewed. Patient characteristics, mechanism of injury, intervention, and associated organ injuries were compared between those with and without BAGI.

RESULTS

Blunt adrenal gland injury was identified in 38 of 262 patients (14.5%). The right side was the predominant site of injury (68%). There were no differences in vital sign, in-hospital mortality, intervention, and concomitant abdominal organ injuries between those with and without adrenal gland injury. Patients with BAGI had a higher frequency of fall and motorcycle collision as mechanisms of injury. In addition, patients with BAGI had a higher injury severity score and a higher frequency of concomitant severe head, chest, and pelvic injuries.

CONCLUSION

The results of the present study suggest that the deceleration injury leading to concomitant head, chest, or pelvic injuries with blunt abdominal trauma may be associated with the mechanism of BAGI.

LEVEL OF EVIDENCE

Prognostic study, level IV.
The microbiome of the nasopharynx
Authors: Flynn Matthew , Dooley James
Published: June 2021

The nasopharyngeal microbiome is a dynamic microbial interface of the aerodigestive tract, and a diagnostic window in the fight against respiratory infections and antimicrobial resistance. As its constituent bacteria, viruses and mycobacteria become better understood and sampling accuracy improves, diagnostics of the nasopharynx could guide more personalized care of infections of surrounding areas including the lungs, ears and sinuses. This review will summarize the current literature from a clinical perspective and highlight its growing importance in diagnostics and infectious disease management.
Systematic single-variant and gene-based association testing of thousands of phenotypes in 426,370 UK Biobank exomes
Authors: Karczewski Konrad J. , Solomonson Matthew , Chao Katherine R. , Goodrich Julia K. , Tiao Grace , Lu Wenhan , Riley-Gillis Bridget M. , Tsai Ellen A. , Kim Hye In , Zheng Xiuwen , Rahimov Fedik , Esmaeeli Sahar , Grundstad A. Jason , Reppell Mark , Waring Jeff , Jacob Howard , Sexton David , Bronson Paola G. , Chen Xing , Hu Xinli , Goldstein Jacqueline I. , King Daniel , Vittal Christopher , Poterba Timothy , Palmer Duncan S. , Churchhouse Claire , Howrigan Daniel P. , Zhou Wei , Watts Nicholas A. , Nguyen Kevin , Nguyen Huy , Mason Cara , Farnham Christopher , Tolonen Charlotte , Gauthier Laura D. , Gupta Namrata , MacArthur Daniel G. , Rehm Heidi L. , Seed Cotton , Philippakis Anthony A. , Daly Mark J. , Davis J. Wade , Runz Heiko , Miller Melissa R. , Neale Benjamin M.
Published: June 2021

Genome-wide association studies have successfully discovered thousands of common variants associated with human diseases and traits, but the landscape of rare variation in human disease has not been explored at scale. Exome sequencing studies of population biobanks provide an opportunity to systematically evaluate the impact of rare coding variation across a wide range of phenotypes to discover genes and allelic series relevant to human health and disease. Here, we present results from systematic association analyses of 4,529 phenotypes using single-variant and gene tests of 426,370 individuals in the UK Biobank with exome sequence data. We find that the discovery of genetic associations is tightly linked to frequency as well as correlated with metrics of deleteriousness and natural selection. We highlight biological findings elucidated by these data and release the dataset as a public resource alongside the Genebass browser for rapidly exploring rare variant association results.
Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial – BCPP/ Ya Tsie trial
Authors: Magosi Lerato E. , Zhang Yinfeng , Golubchik Tanya , De Gruttola Victor , Tchetgen Eric Tchetgen , Novitsky Vlad , Moore Janet , Bachanas Pam , Segolodi Tebogo , Lebelonyane Refeletswe , Holme Molly Pretorius , Moyo Sikhulile , Makhema Joseph , Lockman Shahin , Fraser Christophe , Essex Max , Lipsitch Marc
Published: June 2021

Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence. To elucidate patterns of HIV spread in universal test-and-treat trials we quantified the contribution of geographic-location, gender, age and randomized-HIV- intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana (estimated trial population: 175,664). Deep-sequence phylogenetic analysis revealed that most inferred HIV transmissions within the trial occurred within the same or between neighboring communities, and between similarly-aged partners. Transmissions into intervention communities from control communities were more common than the reverse post-baseline (30% [12.2 – 56.7] versus 3% [0.1 – 27.3]) than at baseline (7% [1.5 – 25.3] versus 5% [0.9 – 22.9]) compatible with a benefit from treatment-as-prevention. Our findings suggest that population mobility patterns are fundamental to HIV transmission dynamics and to the impact of HIV control strategies.
First identification of SARS-CoV-2 Lambda (C.37) variant in Southern Brazil
Authors: Wink Priscila Lamb , Zempulski Volpato Fabiana Caroline , Monteiro Francielle Liz , Willig Julia Biz , Zavascki Alexandre Prehn , Luís Barth Afonso , Martins Andreza Francisco
Published: June 2021

In June 15, 2021, the lineage Lambda (C.37) of SARS-CoV-2 was considered a variant of interest (VOI) by the World Health Organization. This lineage has high prevalence in some South America countries but it was described only occasionally in Brazil. Here we describe the first report of the SARS-CoV-2 Lambda variant in Southern Brazil. The sequence described in this paper presented all the eight C.37 defining lineage mutations (ORF1a gene: Δ3675-3677; Spike gene: Δ246-252, G75V, T76I, L452Q, F490S, D614G, and T859N) in addition to other 19 mutations. Considering that this VOI has been associated with high rates of transmissibility, the possible spread in the Southern Brazilian community is a matter of concern.
Social return on investment of home exercise and community referral for people with early dementia
Authors: Hartfiel Ned , Gladman John , Harwood Rowan , Edwards Rhiannon Tudor
Published: June 2021

Background

Exercise can improve physical function and slow the progression of dementia. However, uncertainty exists around the cost-effectiveness of exercise programmes for people with early dementia.

Objective

The aim is to determine whether a home-based supervised exercise programme (PrAISED – promoting activity, independence, and stability in early dementia) can generate a positive social return on investment (SROI).

Methods

SROI was conducted as part of a randomised controlled feasibility trial comparing PrAISED with usual care. Wellbeing valuation was used to compare the costs of the programme with the monetised benefits to participants, carers, and healthcare service providers.

Results

The PrAISED programme generated SROI ratios ranging from £3.46 to £5.94 for every £1 invested. Social value was created from improved physical activity, increased confidence, more social connection and PrAISED participants using healthcare services less often than usual care.

Conclusion

Home-based supervised exercise programmes can generate a positive SROI for people with early dementia.

Trial registration

ClinicalTrials.gov: NCT02874300 (first posted 22nd August 2016), ISRCTN: 10550694 (date assigned 31st August 2016)
Moving Beyond the ‘CAP’ of the Iceberg: Intrinsic Connectivity Networks in fMRI are Continuously Engaging and Overlapping
Authors: Iraji A. , Faghiri A. , Fu Z. , Kochunov P. , Adhikari B. M. , Belger A. , Ford J.M. , McEwen S. , Mathalon D.H. , Pearlson G.D. , Potkin S.G. , Preda A. , Turner J.A. , van Erp T.G.M. , Chang C. , Calhoun V.D.
Published: June 2021

Resting-state functional magnetic resonance imaging is currently the mainstay of functional neuroimaging and has allowed researchers to identify intrinsic connectivity networks (aka functional networks) at different spatial scales. However, little is known about the temporal profiles of these networks and whether it is best to model them as continuous phenomena in both space and time or, rather, as a set of temporally discrete events. Both categories have been supported by series of studies with promising findings. However, a critical question is whether focusing only on time points presumed to contain isolated neural events and disregarding the rest of the data is missing important information, potentially leading to misleading conclusions. In this work, we argue that brain networks identified within the spontaneous blood oxygenation level-dependent (BOLD) signal are not limited to temporally sparse burst moments and that these event present time points (EPTs) contain valuable but incomplete information about the underlying functional patterns.

We focus on the default mode and show evidence that is consistent with its continuous presence in the BOLD signal, including during the event absent time points (EATs), i.e., time points that exhibit minimum activity and are the least likely to contain an event. Moreover, our findings suggest that EPTs may not contain all the available information about their corresponding networks. We observe distinct default mode connectivity patterns obtained from all time points (AllTPs), EPTs, and EATs. We show evidence of robust relationships with schizophrenia symptoms that are both common and unique to each of the sets of time points (AllTPs, EPTs, EATs), likely related to transient patterns of connectivity. Together, these findings indicate the importance of leveraging the full temporal data in functional studies, including those using event-detection approaches.
Unsupervised classification of SARS-CoV-2 genomic sequences uncovers hidden genetic diversity and suggests an efficient strategy for genomic surveillance
Authors: Chiara Matteo , Horner David S. , Ferrandi Erika , Gissi Carmela , Pesole Graziano
Published: June 2021

Accurate and timely monitoring of emerging genomic diversity is crucial for limiting the spread of potentially more transmissible/pathogenic strains of SARS-CoV-2. At the time of writing, over 1.8M distinct viral genome sequences have been made publicly available, and a sophisticated nomenclature system based on phylogenetic evidence and expert manual curation has allowed the relatively rapid classification of emerging lineages of potential concern.

Here, we propose a complementary approach that integrates fine-grained spatiotemporal estimates of allele frequency with unsupervised clustering of viral haplotypes, and demonstrate that multiple highly frequent genetic variants, arising within large and/or rapidly expanding SARS-CoV-2 lineages, have highly biased geographic distributions and are not adequately captured by current SARS-CoV-2 nomenclature standards.

Our results advocate a partial revision of current methods used to track SARS-CoV-2 genomic diversity and highlight the importance of the application of strategies based on the systematic analysis and integration of regional data. Here we provide a complementary, completely automated and reproducible framework for the mapping of genetic diversity in time and across different geographic regions, and for the prioritization of virus variants of potential concern. We believe that the approach outlined in this study will contribute to relevant advances to current genomic surveillance methods.