Prenatal exposure to environmental toxins and comprehensive dental findings in a population cohort of children.

Environmental toxins are known to have many impacts on growth and development in humans, starting in utero. Alterations in amelogenesis, caused by chemical and physical trauma that occur during the antenatal, perinatal and postnatal time periods, may result in developmental defects in deciduous and permanent tooth enamel, as demonstrated in animal studies. These defects can be clinically visible and result in a variety of morphological and functional problems in the dentition. Since enamel does not remodel after formation, it may serve as a permanent record of insults during organ development.Our primary purpose was to investigate any possible relationship between intrauterine exposure to endocrine disrupting chemicals (phenols and phthalates) and developmental defects in enamel in children, while also accounting for fluoride exposure. Our secondary purpose was to report descriptively on findings from comprehensive dental examinations performed on 356 children that were drawn from the general paediatric population. A cohort of children from the Utah Children's Project (N = 356) that had full medical exams, comprehensive medical and family histories and available biospecimens were given extraoral and intraoral examinations. They also completed an oral health questionnaire. Standardized intraoral photographs were taken of the teeth and viewed by standardised examiners and the dental observations were recorded for a full inventory of findings, including: tooth morphology, caries, restorations, colorations, attrition, erosion, fractures and hypomineralization. Perinatal maternal urine samples were assessed for the concentration of fluoride, phenols and phthalates, including bisphenol A (BPA).Pairwise statistical analyses were done to correlate the dental findings with one another and with the presence of environment chemicals found in the urine samples. Hypomineralization was the most common finding (96% of children; 37% of deciduous teeth, 42% of permanent teeth), consistent with molar incisor hypomineralization (MIH) described in other human populations. No consistent correlations were seen between dental findings and the presence of phenols and phthalates in prenatal urine, but the number of samples available for the assessment was limited (n = 35).In conclusion, we found a high proportion of dental hypomineralization in a population based paediatric cohort, but did not find an association with prenatal exposure to phenols and phthalates.

Mental health outcomes in a population-based cohort of patients with prostate cancer.

BACKGROUND: Few studies have evaluated mental health disorders comprehensively among patients with prostate cancer on long-term follow-up. The primary aim of our study was to assess the incidence of mental health disorders among patients with prostate cancer compared with a general population cohort. A secondary aim was to investigate potential risk factors for mental health disorders among patients with prostate cancer. METHODS: Cohorts of 18 134 patients with prostate adenocarcinomas diagnosed between 2004 and 2017 and 73470 men without cancer matched on age, birth state, and follow-up time were identified. Mental health diagnoses were identified from electronic health records and statewide health-care facilities data. Cox proportional hazard models were used to estimate hazard ratios. All statistical tests were 2-sided. RESULTS: The hazard ratios for mood disorders, including depression, among prostate cancer survivors increased for all follow-up periods compared with the general population. The hazard ratios for any mental illness increased with Hispanic, Black, or multiple races; people who were underweight or obese; those with advanced prostate cancer; and those undergoing their first course cancer treatment. We also observed statistically significantly increased hazard ratios for mental health disorders among patients with lower socioeconomic status (P < .0001) and increasing duration of androgen-deprivation therapy (P = .0348). Prostate cancer survivors had a 61% increased hazard ratio for death with a depression diagnosis. CONCLUSION: Prostate cancer diagnosis was associated with a higher risk of mental health disorders compared with the general population, which was observed as long as 10-16 years after cancer diagnosis. Providing long-term mental health support may be beneficial to increasing life expectancy for patients with prostate cancer.

Alcohol consumption and opioid craving among chronic pain patients prescribed long-term opioid therapy.

BACKGROUND: Concurrent use of alcohol with opioids is common among chronic pain patients, heightening the risk for disordered opioid use and overdose, yet the relationship between alcohol consumption and opioid craving among chronic pain patients remains largely unexplored. Here we examined the relationship between alcohol consumption and opioid craving among chronic pain patients on long-term opioid therapy. METHODS: A cross-sectional study was conducted with 335 chronic pain patients on long-term opioid therapy. Participants completed the Timeline Followback to assess alcohol consumption, as well as measures of opioid craving, pain severity, and pain interference. Linear regression analyses examined the relationship between alcohol consumption and opioid craving, controlling for pain severity, pain interference, and opioid misuse severity. RESULTS: Alcohol consumption (total number of drinks and amount consumed in one sitting) was positively associated with opioid craving (p < 0.001 and p = 0.005, respectively). Pain severity did not predict opioid craving. The relationship between alcohol consumption and opioid craving remained significant after controlling for pain severity, pain interference, and opioid misuse severity. CONCLUSION: Alcohol consumption is linked with more severe opioid craving among chronic pain patients prescribed long-term opioid therapy. Patients receiving opioid analgesics should be carefully screened for co-use of alcohol.

Effectiveness of Self-Collected, Ambient Temperature-Preserved Nasal Swabs Compared to Samples Collected by Trained Staff for Genotyping of Respiratory Viruses by Shotgun RNA Sequencing: Comparative Study.

BACKGROUND: The SARS-CoV-2 pandemic has underscored the need for field specimen collection and transport to diagnostic and public health laboratories. Self-collected nasal swabs transported without dependency on a cold chain have the potential to remove critical barriers to testing, expand testing capacity, and reduce opportunities for exposure of health professionals in the context of a pandemic. OBJECTIVE: We compared nasal swab collection by study participants from themselves and their children at home to collection by trained research staff. METHODS: Each adult participant collected 1 nasal swab, sampling both nares with the single swab, after which they collected 1 nasal swab from 1 child. After all the participant samples were collected for the household, the research staff member collected a separate single duplicate sample from each individual. Immediately after the sample collection, the adult participants completed a questionnaire about the acceptability of the sampling procedures. Swabs were placed in temperature-stable preservative and respiratory viruses were detected by shotgun RNA sequencing, enabling viral genome analysis. RESULTS: In total, 21 households participated in the study, each with 1 adult and 1 child, yielding 42 individuals with paired samples. Study participants reported that self-collection was acceptable. Agreement between identified respiratory viruses in both swabs by RNA sequencing demonstrated that adequate collection technique was achieved by brief instructions. CONCLUSIONS: Our results support the feasibility of a scalable and convenient means for the identification of respiratory viruses and implementation in pandemic preparedness for novel respiratory pathogens.

Comparing Active Surveillance and Watchful Waiting With Radical Treatment Using Machine Learning Models Among Patients With Prostate Cancer.

PURPOSE: In 2021, 59.6% of low-risk patients with prostate cancer were under active surveillance (AS) as their first course of treatment. However, few studies have investigated AS and watchful waiting (WW) separately. The objectives of this study were to develop and validate a population-level machine learning model for distinguishing AS and WW in the conservative treatment group, and to investigate initial cancer management trends from 2004 to 2017 and the risk of chronic diseases among patients with prostate cancer with different treatment modalities. METHODS: In a cohort of 18,134 patients with prostate adenocarcinoma diagnosed between 2004 and 2017, 1,926 patients with available AS/WW information were analyzed using machine learning algorithms with 10-fold cross-validation. Models were evaluated using performance metrics and Brier score. Cox proportional hazard models were used to estimate hazard ratios for chronic disease risk. RESULTS: Logistic regression models achieved a test area under the receiver operating curve of 0.73, F-score of 0.79, accuracy of 0.71, and Brier score of 0.29, demonstrating good calibration, precision, and recall values. We noted a sharp increase in AS use between 2004 and 2016 among patients with low-risk prostate cancer and a moderate increase among intermediate-risk patients between 2008 and 2017. Compared with the AS group, radical treatment was associated with a lower risk of prostate cancer-specific mortality but higher risks of Alzheimer disease, anemia, glaucoma, hyperlipidemia, and hypertension. CONCLUSION: A machine learning approach accurately distinguished AS and WW groups in conservative treatment in this decision analytical model study. Our results provide insight into the necessity to separate AS and WW in population-based studies.

Resolution of stuttering during ketamine treatment: a case report.

BACKGROUND: Stuttering may include repetition of words in whole or part, difficulty saying words, and elongated pauses in speech. Approximately 5% of children stutter for a period lasting 6 months or more. Most of those children stop stuttering as they approach adulthood, but the condition persists in approximately 1% of adults. The cause of stuttering is unknown. Adults who stutter face substantial burdens in many aspects of their lives. Stutterers may choose not to pursue meaningful employment opportunities, may not be hired for positions they seek, or may be denied promotions or positive performance evaluations. Stuttering can cause physical tension from fear of speaking. Social challenges arise when a person who stutters is seen as less capable or of lower intelligence than fluent speakers. Stuttering causes emotional difficulties through the frustration and embarrassment that disfluent speakers feel. Stutterers may experience a general loss of self-esteem and personal satisfaction in life. Speech therapy is the primary intervention for stuttering. Medications have been investigated as treatments for stuttering, but no medication has been identified that has widespread effectiveness. CASE PRESENTATION: A 60-year-old white non-Hispanic woman who had been a near lifelong stutterer was prescribed ketamine for an unrelated condition and experienced an almost immediate resolution of her stuttering. CONCLUSIONS: Many possible pharmacological treatments for stuttering have been studied. Some medications appear to be effective in some patients; some appear to be more generally effective but have negative side effects. No reporting in relevant literature has addressed a possible role for ketamine in stuttering treatment. On the basis of this case report, research on the effect of ketamine on stuttering would be useful. Any effective treatment for stuttering would have a significant positive effect on quality of life for persons who stutter.

Prenatal depression and risk of child autism-related traits among participants in the Environmental influences on Child Health Outcomes program.

This study evaluated the association between prenatal depression and offspring autism-related traits. The sample comprised 33 prenatal/pediatric cohorts participating in the Environmental influences on Child Health Outcomes program who contributed information on prenatal depression and autism-related traits. Autism-related traits were assessed continuously and at the diagnostic cut-off using the Social Responsiveness Scale for children up to 12 years of age. Main analyses included 3994 parent-child pairs with prenatal depression diagnoses data; secondary analyses included 1730 parent-child pairs with depression severity data. After confounder adjustment, we observed an increase in autism-related traits among children of individuals with prenatal depression compared to those without (adjusted ß = 1.31 95% CI: 0.65, 1.98). Analyses stratified by child sex documented a similar significant association among boys (aß = 1.34 95%CI: 0.36, 2.32) and girls (aß = 1.26 95% CI: 0.37, 2.15). Prenatal depression was also associated with increased odds of moderate to severe autism-related traits (adjusted odds ratio: 1.64, 95%CI: 1.09, 2.46), the screening threshold considered high risk of autism spectrum disorder (ASD) diagnosis. Findings highlight the importance of prenatal depression screening and preventive interventions for children of pregnant individuals with depression to support healthy development. Future research is needed to clarify whether these findings reflect overlap in genetic risk for depression and ASD-related traits or another mechanism.

Sociodemographic Differences in COVID-19 Pandemic Experiences Among Families in the United States.

Importance: Few population-based studies in the US collected individual-level data from families during the COVID-19 pandemic. Objective: To examine differences in COVID-19 pandemic-related experiences in a large sociodemographically diverse sample of children and caregivers. Design, Setting, and Participants: The Environmental influences on Child Health Outcomes (ECHO) multi-cohort consortium is an ongoing study that brings together 64 individual cohorts with participants (24 757 children and 31 700 caregivers in this study) in all 50 US states and Puerto Rico. Participants who completed the ECHO COVID-19 survey between April 2020 and March 2022 were included in this cross-sectional analysis. Data were analyzed from July 2021 to September 2022. Main Outcomes and Measures: Exposures of interest were caregiver education level, child life stage (infant, preschool, middle childhood, and adolescent), and urban or rural (population <50 000) residence. Dependent variables included COVID-19 infection status and testing; disruptions to school, child care, and health care; financial hardships; and remote work. Outcomes were examined separately in logistic regression models mutually adjusted for exposures of interest and race, ethnicity, US Census division, sex, and survey administration date. Results: Analyses included 14 646 children (mean [SD] age, 7.1 [4.4] years; 7120 [49%] female) and 13 644 caregivers (mean [SD] age, 37.6 [7.2] years; 13 381 [98%] female). Caregivers were racially (3% Asian; 16% Black; 12% multiple race; 63% White) and ethnically (19% Hispanic) diverse and comparable with the US population. Less than high school education (vs master's degree or more) was associated with more challenges accessing COVID-19 tests (adjusted odds ratio [aOR], 1.88; 95% CI, 1.06-1.58), lower odds of working remotely (aOR, 0.04; 95% CI, 0.03-0.07), and more food access concerns (aOR, 4.14; 95% CI, 3.20-5.36). Compared with other age groups, young children (age 1 to 5 years) were least likely to receive support from schools during school closures, and their caregivers were most likely to have challenges arranging childcare and concerns about work impacts. Rural caregivers were less likely to rank health concerns (aOR, 0.77; 95% CI, 0.69-0.86) and social distancing (aOR, 0.82; 95% CI, 0.73-0.91) as top stressors compared with urban caregivers. Conclusions: Findings in this cohort study of US families highlighted pandemic-related burdens faced by families with lower socioeconomic status and young children. Populations more vulnerable to public health crises should be prioritized in recovery efforts and future planning.

Adverse Health Outcomes among Rural and Urban Breast Cancer Survivors: A Population-Based Cohort Study.

BACKGROUND: Limited population-based studies have focused on breast cancer survivors in rural populations. We sought to evaluate the risk of adverse health outcomes among rural and urban breast cancer survivors and to evaluate potential predictors for the highest risk outcomes. METHODS: A population-based cohort of rural and urban breast cancer survivors diagnosed between 1997 and 2017 was identified in the Utah Cancer Registry (UCR). Rural breast cancer survivors were matched on year (±1 year) and age at cancer diagnosis (±1 year) with up to 5 urban breast cancer survivors (2,359 rural breast cancer survivors; 11,748 urban breast cancer survivors). Cox proportional hazards models were used to calculate HRs with 99% confidence intervals (CI) for adverse health outcomes overall, within 5 years, and >5 years after cancer diagnosis. RESULTS: Compared with urban breast cancer survivors, rural breast cancer survivors had a 39% (HR, 1.39; 95% CI, 1.02-1.65) higher risk of heart failure (HF) within the 5 years of follow-up. Overall, there was no increase in the risk of other evaluated adverse health outcomes. A higher baseline body mass index and Charlson Comorbidity Index, family history of cardiovascular diseases, family history of breast cancer, and advanced cancer stage were risk factors for HF for rural and urban breast cancer survivors, with similar levels of HF risk. CONCLUSIONS: Rural residence was associated with an increased risk of HF among breast cancer survivors. IMPACT: Our study highlights the need for primary preventive strategies for rural cancer survivors at risk of heart failure.

Generating Older Adult Multimorbidity Trajectories Using Various Comorbidity Indices and Calculation Methods.

Background and Objectives: Older adult multimorbidity trajectories are helpful for understanding the current and future health patterns of aging populations. The construction of multimorbidity trajectories from comorbidity index scores will help inform public health and clinical interventions targeting those individuals that are on unhealthy trajectories. Investigators have used many different techniques when creating multimorbidity trajectories in prior literature, and no standard way has emerged. This study compares and contrasts multimorbidity trajectories constructed from various methods. Research Design and Methods: We describe the difference between aging trajectories constructed with the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). We also explore the differences between acute (single-year) and chronic (cumulative) derivations of CCI and ECI scores. Social determinants of health can affect disease burden over time; thus, our models include income, race/ethnicity, and sex differences. Results: We use group-based trajectory modeling (GBTM) to estimate multimorbidity trajectories for 86,909 individuals aged 66-75 in 1992 using Medicare claims data collected over the following 21 years. We identify low-chronic disease and high-chronic disease trajectories in all 8 generated trajectory models. Additionally, all 8 models satisfied prior established statistical diagnostic criteria for well-performing GBTM models. Discussion and Implications: Clinicians may use these trajectories to identify patients on an unhealthy path and prompt a possible intervention that may shift the patient to a healthier trajectory.

Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Responses After Community Infections in Children and Adults.

Background: We compared postinfection severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (nAb) responses among children and adults while the D614G-like strain and Alpha, Iota, and Delta variants circulated. Methods: During August 2020-October 2021, households with adults and children were enrolled and followed in Utah, New York City, and Maryland. Participants collected weekly respiratory swabs that were tested for SARS-CoV-2 and had sera collected during enrollment and follow-up. Sera were tested for SARS-CoV-2 nAb by pseudovirus assay. Postinfection titers were characterized with biexponential decay models. Results: Eighty participants had SARS-CoV-2 infection during the study (47 with D614G-like virus, 17 with B.1.1.7, and 8 each with B.1.617.2 and B.1.526 virus). Homologous nAb geometric mean titers (GMTs) trended higher in adults (GMT = 2320) versus children 0-4 (GMT = 425, P = .33) and 5-17 years (GMT = 396, P = .31) at 1-5 weeks postinfection but were similar from 6 weeks. Timing of peak titers was similar by age. Results were consistent when participants with self-reported infection before enrollment were included (n = 178). Conclusions: The SARS-CoV-2 nAb titers differed in children compared to adults early after infection but were similar by 6 weeks postinfection. If postvaccination nAb kinetics have similar trends, vaccine immunobridging studies may need to compare nAb responses in adults and children 6 weeks or more after vaccination.

Indoor and outdoor air pollution and couple fecundability: a systematic review.

BACKGROUND: Air pollution is both a sensory blight and a threat to human health. Inhaled environmental pollutants can be naturally occurring or human-made, and include traffic-related air pollution (TRAP), ozone, particulate matter (PM) and volatile organic compounds, among other substances, including those from secondhand smoking. Studies of air pollution on reproductive and endocrine systems have reported associations of TRAP, secondhand smoke (SHS), organic solvents and biomass fueled-cooking with adverse birth outcomes. While some evidence suggests that air pollution contributes to infertility, the extant literature is mixed, and varying effects of pollutants have been reported. OBJECTIVE AND RATIONALE: Although some reviews have studied the association between common outdoor air pollutants and time to pregnancy (TTP), there are no comprehensive reviews that also include exposure to indoor inhaled pollutants, such as airborne occupational toxicants and SHS. The current systematic review summarizes the strength of evidence for associations of outdoor air pollution, SHS and indoor inhaled air pollution with couple fecundability and identifies gaps and limitations in the literature to inform policy decisions and future research. SEARCH METHODS: We performed an electronic search of six databases for original research articles in English published since 1990 on TTP or fecundability and a number of chemicals in the context of air pollution, inhalation and aerosolization. Standardized forms for screening, data extraction and study quality were developed using DistillerSR software and completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of both air pollution and fecundability studies. OUTCOMES: The search returned 5200 articles, 4994 of which were excluded at the level of title and abstract screening. After full-text screening, 35 papers remained for data extraction and synthesis. An additional 3 papers were identified independently that fit criteria, and 5 papers involving multiple routes of exposure were removed, yielding 33 articles from 28 studies for analysis. There were 8 papers that examined outdoor air quality, while 6 papers examined SHS exposure and 19 papers examined indoor air quality. The results indicated an association between outdoor air pollution and reduced fecundability, including TRAP and specifically nitrogen oxides and PM with a diameter of ≤2.5 µm, as well as exposure to SHS and formaldehyde. However, exposure windows differed greatly between studies as did the method of exposure assessment. There was little evidence that exposure to volatile solvents is associated with reduced fecundability. WIDER IMPLICATIONS: The evidence suggests that exposure to outdoor air pollutants, SHS and some occupational inhaled pollutants may reduce fecundability. Future studies of SHS should use indoor air monitors and biomarkers to improve exposure assessment. Air monitors that capture real-time exposure can provide valuable insight about the role of indoor air pollution and are helpful in assessing the short-term acute effects of pollutants on TTP.

Characteristics associated with the availability of therapeutic acupuncture in substance use disorder treatment facilities in the United States.

BACKGROUND: We examine the characteristics associated with the availability of therapeutic acupuncture in substance use disorder (SUD) treatment facilities in the United States (US). METHODS: This study utilizes data from the 2018 National Survey of Substance Abuse Treatment Services (N-SSATS). Multivariable logistic regression was performed. RESULTS: Only 5.5% (n = 814) of all SUD treatment facilities offered acupuncture therapy. Facilities operating an opioid treatment program (OTP) were 1.60 times more likely to offer therapeutic acupuncture than non-OTP facilities. Facilities that offered oral naltrexone pharmacotherapy or buprenorphine with naloxone pharmacotherapy were 1.63 and 1.37 times more likely to offer therapeutic acupuncture, respectively, compared to facilities that did not offer these pharmacotherapies. Federal government facilities were over four times more likely to offer acupuncture than those operated by state governments and had triple the odds of having acupuncture than private nonprofit organizations. Tribal facilities were over five times more likely than state government-operated facilities to offer acupuncture. Facilities located in the Western region of the US were 1.59, 1.39, and 1.30 times more likely than Northeastern, Midwestern, and Southern US regions, respectively, to offer acupuncture therapy. CONCLUSIONS: Although complementary and holistic approaches such as acupuncture are accepted adjunct methods to treat persons with SUD, the findings suggest that their utilization in SUD treatment facilities in the US is minimal. Results, however, highlight that facilities operated by tribal and federal governments, those that are located in the Western region of the US, and non-hospital facilities have the highest odds of incorporating therapeutic acupuncture as treatment for SUD.Supplemental data for this article is available online at https://doi.org/10.1080/10550887.2022.2056401 .

Factors Associated with Intention to Vaccinate Children 0-11 Years of Age Against COVID-19.

BACKGROUND: Millions of children have tested positive for SARS-CoV-2, and over 1000 children have died in the US. However, vaccination rates for children 5 to 11 years old are low. METHODS: Starting in August 2020, we conducted a prospective SARS-CoV-2 household surveillance study in Spanish and English-speaking households in New York City and Utah. From October 21 to 25, 2021, we asked caregivers about their likelihood of getting COVID-19 vaccine for their child, and reasons that they might or might not vaccinate that child. We compared intent to vaccinate by site, demographic characteristics, SARS-CoV-2 infection detected by study surveillance, and parents' COVID-19 vaccination status using Chi-square tests and a multivariable logistic regression model, accounting for within-household clustering. RESULTS: Among parents or caregivers of 309 children (0 to 11 years) in 172 households, 87% were very or somewhat likely to intend to vaccinate their child. The most prevalent reasons for intending to vaccinate were to protect family and friends and the community; individual prevention was mentioned less often. The most prevalent reasons for not intending to vaccinate were side effect concerns and wanting to wait and see.In multivariable analysis, parents had much lower odds of intending to vaccinate if someone in the household had tested SARS-CoV-2-positive during the study (adjusted odds ratio = 0.09; 95% confidence interval, 0.03-0.3). CONCLUSION: This study highlighted several themes for clinicians and public health officials to consider including the importance and safety of vaccination for this age-group even if infected previously, and the benefits of vaccination to protect family, friends, and community.

Does a short luteal phase correlate with an increased risk of miscarriage? A cohort study.

BACKGROUND: Miscarriage is defined as spontaneous loss of pregnancy prior to 20 weeks gestation. With an estimated risk of 15% of clinically confirmed pregnancies ending in miscarriage, it is the most common adverse event in pregnancy. Woman's age is the primary risk factor for miscarriage, while medical conditions, including hormonal abnormalities, are also associated. Progesterone is essential for maintaining pregnancy. A short luteal phase may reflect inadequate levels of progesterone production, but it is unclear whether a short luteal phase correlates with an increase in the risk of miscarriage. METHODS: Using a cohort study design, we conducted a secondary data analysis from four cohorts of couples who used a standardized protocol to track biomarkers of the female cycles. A short luteal phase was defined as less than 10 days, with < 11, < 9, and < 8 days as alternate definitions in sensitivity analyses. We included women who experienced a pregnancy with a known outcome, identified the length of the luteal phase in up to 3 cycles prior to conception and assessed the relationship with miscarriage using a modified Poisson regression analysis, adjusting for demographic characteristics, smoking, alcohol use and previous pregnancy history. RESULTS: In our sample of 252 women; the overall miscarriage rate was 18.7%. The adjusted incident risk ratio of miscarriage in women who had at least one short luteal phase < 10 days, compared to those who had none, was 1.01 (95% CI: 0.57, 1.80) Similar null risk was found when assessing alternative lengths of short luteal phase. Women who had short luteal phases < 10 days in all 3 cycles prior to the conception cycle had an incident risk ratio of 2.14 (95% CI: 0.7, 6.55). CONCLUSIONS: Our study found that a short luteal phase in the three cycles prior to conception was not associated with higher rates of miscarriage in an international cohort of women tracking their cycles, but our sample size was limited. Further research to determine if short luteal phases or luteal phase deficiency is associated with early pregnancy losses among preconception cohorts with daily tracking of cycle parameters, in addition to progesterone and human chorionic gonadotropin levels, is warranted. Additionally, future studies should include women with recurrent short luteal phases as a more likely risk factor than isolated short luteal phases.

This study looks at whether women have a higher risk of miscarriage if the second half of their menstrual or reproductive cycle is shorter than normal. The second half of the cycle, referred to as the luteal phase, is normally 11 to 16 days long. If the luteal phase is too short this may suggest a woman does not have enough progesterone, the hormone essential for maintaining pregnancy.This study included 252 pregnant women for whom we had data on the length of at least one luteal phase prior to pregnancy and for whom we knew the outcome of the pregnancy. Almost one-fifth of the women in our study had a miscarriage. However, we found there was no difference in the risk for miscarriage if women had a short or a normal luteal phase.

SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference.

The reliability of sequence-based inference of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with a reverse transcription-PCR cycle threshold of ≤30 underwent whole-genome sequencing. Intrahost single-nucleotide variants (iSNV) were identified at a ≥5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole-genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had ≥1 consensus sequence that differed by 1 to 2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and in 6 of 11 with distinct ones. In multiple-infection households, whole-genome consensus sequences differed by 0 to 1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. IMPORTANCE We performed whole-genome sequencing of SARS-CoV-2 from prospectively identified cases in three longitudinal household cohorts. In a majority of multi-infection households, SARS-CoV-2 consensus sequences were indistinguishable, and they differed by 1 to 2 mutations in the rest. Importantly, even with modest genomic surveillance of the community (3 to 5% of cases sequenced), it was not uncommon to find community sequences interspersed with household sequences on phylogenetic trees. Identification of shared minority variants only occasionally resolved these ambiguities in transmission linkage. Overall, the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. Our work highlights the need to carefully consider both epidemiologic linkage and sequence data to define transmission chains in households, hospitals, and other transmission settings.

Impact of Age and Symptom Development on SARS-CoV-2 Transmission in Households With Children-Maryland, New York, and Utah, August 2020-October 2021.

Background: Households are common places for spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated factors associated with household transmission and acquisition of SARS-CoV-2. Methods: Households with children age <18 years were enrolled into prospective, longitudinal cohorts and followed from August 2020 to August 2021 in Utah, September 2020 to August 2021 in New York City, and November 2020 to October 2021 in Maryland. Participants self-collected nasal swabs weekly and with onset of acute illness. Swabs were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. We assessed factors associated with SARS-CoV-2 acquisition using a multilevel logistic regression adjusted for household size and clustering and SARS-CoV-2 transmission using a logistic regression adjusted for household size. Results: Among 2053 people (513 households) enrolled, 180 people (8.8%; in 76 households) tested positive for SARS-CoV-2. Compared with children age <12 years, the odds of acquiring infection were lower for adults age ≥18 years (adjusted odds ratio [aOR], 0.34; 95% CI, 0.14-0.87); however, this may reflect vaccination status, which protected against SARS-CoV-2 acquisition (aOR, 0.17; 95% CI, 0.03-0.91). The odds of onward transmission were similar between symptomatic and asymptomatic primary cases (aOR, 1.00; 95% CI, 0.35-2.93) and did not differ by age (12-17 years vs <12 years: aOR, 1.08; 95% CI, 0.20-5.62; ≥18 years vs <12 years: aOR, 1.70; 95% CI, 0.52-5.83). Conclusions: Adults had lower odds of acquiring SARS-CoV-2 compared with children, but this association might be influenced by coronavirus disease 2019 (COVID-19) vaccination, which was primarily available for adults and protective against infection. In contrast, all ages, regardless of symptoms and COVID-19 vaccination, had similar odds of transmitting SARS-CoV-2. Our findings underscore the importance of SARS-CoV-2 mitigation measures for persons of all ages.

Detection and Stability of SARS-CoV-2 in Three Self-Collected Specimen Types: Flocked Midturbinate Swab (MTS) in Viral Transport Media, Foam MTS, and Saliva.

Respiratory specimen collection materials shortages hampers severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. We compared specimen alternatives and evaluated SARS-CoV-2 RNA stability under simulated shipping conditions. We compared concordance of RT-PCR detection of SARS-CoV-2 from flocked midturbinate swabs (MTS) in viral transport media (VTM), foam MTS without VTM, and saliva. Specimens were collected between August 2020 and April 2021 from three prospective cohorts. We compared RT-PCR cycle quantification (Cq) for Spike (S), Nucleocapsid (N), and the Open Reading Frame 1ab (ORF) genes for flocked MTS and saliva specimens tested before and after exposure to a range of storage temperatures (4-30°C) and times (2, 3, and 7 days). Of 1,900 illnesses with ≥2 specimen types tested, 335 (18%) had SARS-CoV-2 detected in ≥1 specimen; 304 (91%) were concordant across specimen types. Among illnesses with SARS-CoV-2 detection, 97% (95% confidence interval [CI]: 94-98%) were positive on flocked MTS, 99% (95% CI: 97-100%) on saliva, and 89% (95% CI: 84-93%) on foam MTS. SARS-CoV-2 RNA was detected in flocked MTS and saliva stored up to 30°C for 7 days. All specimen types provided highly concordant SARS-CoV-2 results. These findings support a range of viable options for specimen types, collection, and transport methods that may facilitate SARS-CoV-2 testing during supply and personnel shortages. IMPORTANCE Findings from this analysis indicate that (1) self-collection of flocked and foam MTS and saliva samples is feasible in both adults and children, (2) foam MTS with VTM and saliva are both viable and reasonable alternatives to traditional flocked MTS in VTM for SARS-CoV-2 detection, and (3) these sample types may be stored and transported at ambient temperatures for up to 7 days without compromising sample quality. These findings support methods of sample collection for SARS-CoV-2 detection that may facilitate widespread community testing in the setting of supply and personnel shortages during the current pandemic.

Fertility Awareness-Based Methods for Women's Health and Family Planning.

Background: Fertility awareness-based methods (FABMs) educate about reproductive health and enable tracking and interpretation of physical signs, such as cervical fluid secretions and basal body temperature, which reflect the hormonal changes women experience on a cyclical basis during the years of ovarian activity. Some methods measure relevant hormone levels directly. Most FABMs allow women to identify ovulation and track this "vital sign" of the menstrual or female reproductive cycle, through daily observations recorded on cycle charts (paper or electronic). Applications: Physicians can use the information from FABM charts to guide the diagnosis and management of medical conditions and to support or restore healthy function of the reproductive and endocrine systems, using a restorative reproductive medical (RRM) approach. FABMs can also be used by couples to achieve or avoid pregnancy and may be most effective when taught by a trained instructor. Challenges: Information about individual FABMs is rarely provided in medical education. Outdated information is widespread both in training programs and in the public sphere. Obtaining accurate information about FABMs is further complicated by the numerous period tracking or fertility apps available, because very few of these apps have evidence to support their effectiveness for identifying the fertile window, for achieving or preventing pregnancy. Conclusions: This article provides an overview of different types of FABMs with a published evidence base, apps and resources for learning and using FABMs, the role FABMs can play in medical evaluation and management, and the effectiveness of FABMs for family planning, both to achieve or to avoid pregnancy.

Cardiovascular disease risk in long-term breast cancer survivors: A population-based cohort study.

BACKGROUND: Breast cancer survival is increasing, making late effects such as cardiovascular disease (CVD) more relevant. The purpose of this study was to evaluate incident CVD following breast cancer diagnosis among long-term survivors and to investigate possible risk factors for CVD. METHODS: A population-based cohort of 6641 breast cancer survivors diagnosed between 1997 and 2009 who survived at least 10 years was identified within the Utah Cancer Registry. In addition, 36,612 cancer-free women from the general population, matched by birth year and state, were identified within the Utah Population Database. Cox proportional hazards models were used to calculate CVD hazard ratios (HRs) for >10 to 15 and >15 years. RESULTS: Long-term breast cancer survivors had an increased risk of newly diagnosed diseases of the circulatory system (HR, 1.32; 99% confidence interval [CI], 1.00-1.75) from 10 to 15 years following cancer diagnosis compared with the general population. No increased CVD risks were observed after 15 years. Breast cancer survivors with Charlson Comorbidity Index score ≥2 had a significantly higher risk of diseases of the circulatory system (HR, 2.64; 95% CI, 1.08-6.45) beyond 10 years following breast cancer diagnosis. Similarly, older age, obesity, lower education, and family history of CVD and breast cancer were risk factors for heart and circulatory system diseases among long-term breast cancer survivors. CONCLUSION: Risk of CVD compared to the general population was moderate among this cohort of long-term breast cancer survivors between 10 to 15 years since cancer diagnosis. Awareness of CVD risks is important for breast cancer survivors.