COVID-19 vaccination before or during pregnancy results in high, sustained maternal neutralizing activity to SARS-CoV2 wild-type and Delta/Omicron variants of concern, particularly following a booster dose or infection.

OBJECTIVES: To investigate multi-dose and timings of COVID-19 vaccines in preventing antenatal infection. DESIGN: Prospective observational study investigating primary vaccinations, boosters, antenatal COVID-19 infections, neutralizing antibody (Nab) durability, and cross-reactivity to Delta and Omicron variants of concern (VOCs). RESULTS: 98 patients completed primary vaccination pre-pregnancy (29·6%) and antenatally (63·3%), 24·2% of whom had antenatal COVID-19, while 7·1% were unvaccinated (28·6% had antenatal COVID-19). None had severe COVID-19. Pre-pregnancy vaccination resulted in vaccination-to-infection delay of 23·3 weeks, which extended to 45·2 weeks with a booster, compared to 16·9 weeks following antenatal vaccination (p<0·001). Infections occurred at 26·2 weeks gestation in women vaccinated pre-pregnancy compared to 36·2 weeks gestation in those vaccinated during pregnancy (p<0·007). The risk of COVID-19 infection was higher without antenatal vaccination (hazard ratio 14·6, p=0·05) and after pre-pregnancy vaccination without a booster (hazard ratio 10·4, p=0·002). Antenatal vaccinations initially led to high Nab levels, with mild waning but subsequent rebound. Significant Nab enhancement occurred with a third-trimester booster. Maternal-neonatal Nab transfer was efficient (transfer ratio >1), and cross-reactivity to VOCs was observed. CONCLUSION: Completing vaccination during any trimester delays COVID-19 infection and maintains effective neutralizing activity throughout pregnancy, with robust cross-reactivity to VOCs and efficient maternal-neonatal transfer.

Multisite Pragmatic Cluster-Randomized Controlled Trial of the CONCERN Early Warning System.

Importance: Late predictions of hospitalized patient deterioration, resulting from early warning systems (EWS) with limited data sources and/or a care team's lack of shared situational awareness, contribute to delays in clinical interventions. The COmmunicating Narrative Concerns Entered by RNs (CONCERN) Early Warning System (EWS) uses real-time nursing surveillance documentation patterns in its machine learning algorithm to identify patients' deterioration risk up to 42 hours earlier than other EWSs. Objective: To test our a priori hypothesis that patients with care teams informed by the CONCERN EWS intervention have a lower mortality rate and shorter length of stay (LOS) than the patients with teams not informed by CONCERN EWS. Design: One-year multisite, pragmatic controlled clinical trial with cluster-randomization of acute and intensive care units to intervention or usual-care groups. Setting: Two large U.S. health systems. Participants: Adult patients admitted to acute and intensive care units, excluding those on hospice/palliative/comfort care, or with Do Not Resuscitate/Do Not Intubate orders. Intervention: The CONCERN EWS intervention calculates patient deterioration risk based on nurses' concern levels measured by surveillance documentation patterns, and it displays the categorical risk score (low, increased, high) in the electronic health record (EHR) for care team members. Main Outcomes and Measures: Primary outcomes: in-hospital mortality, LOS; survival analysis was used. Secondary outcomes: cardiopulmonary arrest, sepsis, unanticipated ICU transfers, 30-day hospital readmission. Results: A total of 60 893 hospital encounters (33 024 intervention and 27 869 usual-care) were included. Both groups had similar patient age, race, ethnicity, and illness severity distributions. Patients in the intervention group had a 35.6% decreased risk of death (adjusted hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.532-0.778; P<.0001), 11.2% decreased LOS (adjusted incidence rate ratio, 0.914; 95% CI, 0.902-0.926; P<.0001), 7.5% decreased risk of sepsis (adjusted HR, 0.925; 95% CI, 0.861-0.993; P=.0317), and 24.9% increased risk of unanticipated ICU transfer (adjusted HR, 1.249; 95% CI, 1.093-1.426; P=.0011) compared with patients in the usual-care group. Conclusions and Relevance: A hospital-wide EWS based on nursing surveillance patterns decreased in-hospital mortality, sepsis, and LOS when integrated into the care team's EHR workflow. Trial Registration: ClinicalTrials.gov Identifier: NCT03911687.

Use of Diagnostic Codes for Primary Open-Angle Glaucoma Polygenic Risk Score Construction in Electronic Health Record-linked Biobanks.

PURPOSE: Polygenic risk scores (PRSs) likely predict risk and prognosis of glaucoma. We compared the PRS performance for primary open-angle glaucoma (POAG), defined using International Classification of Diseases (ICD) codes versus manual medical record review. DESIGN: Retrospective cohort study METHODS: We identified POAG cases in Mount Sinai BioMe and Mass General Brigham (MGB) biobank using ICD codes. We confirmed POAG based on optical coherence tomograms and visual fields. In a separate 5% sample, the absence of POAG was confirmed with intraocular pressure and cup-disc ratio criteria. We used genotype data and either self-reported glaucoma diagnoses or ICD-10 codes for glaucoma diagnoses from the UK Biobank and the lassosum method to compute a genome-wide POAG PRS. We compared the area under the curve (AUC) for POAG prediction based on ICD codes versus medical records. RESULTS: We reviewed 804 of 996 BioMe and 367 of 1,006 MGB ICD-identified cases. In BioMe and MGB, respectively: positive predictive value was 53% and 55%; negative predictive value was 96% and 97%; sensitivity was 97% and 97%; and specificity was 44% and 53%. Adjusted PRS AUCs for POAG using ICD codes vs. manual record review in BioMe were not statistically different (p≥0.21) by ancestry: 0.77 vs. 0.75 for African, 0.80 vs. 0.80 for Hispanic, and 0.81 vs. 0.81 for European. Results were similar in MGB (p≥0.18): 0.72 vs. 0.80 for African, 0.83 vs. 0.86 for Hispanic, and 0.74 vs. 0.73 for European. CONCLUSIONS: A POAG PRS performed similarly using either manual review or ICD codes in two EHR-linked biobanks; manual assessment of glaucoma status might be unnecessary for some PRS studies. However, caution should be exercised with using ICD codes for glaucoma diagnosis given their low specificity (44-53%) for manually confirmed cases of glaucoma.

A Cross Sectional Survey of Factors Related to Cannabis Use as a Sleep Aid Among Canadian Cancer Survivors.

OBJECTIVES: Poor sleep is a common side effect of cancer. Cannabis is increasingly used to manage cancer treatment-related symptoms, including sleep. This study investigated factors related to cannabis use for sleep among Canadian cancer survivors. METHOD: Adult Canadian cancer survivors (N = 940) were recruited via the Angus Reid Institute and completed an online, cross-sectional survey. Univariate and multiple binomial logistic regression models identified factors associated with cannabis use for sleep. RESULTS: Of the participants (Mage = 64.5 yrs; Women = 51.1%; White = 92.9%), 25.1% (n = 236) currently use cannabis for sleep. Participants were at greater odds of using cannabis for sleep if they identified as a gender other than man or woman (AOR = 11.132), were diagnosed with multiple medical conditions (2:AOR = 1.988; 3+:AOR = 1.902), two psychological conditions (AOR = 2.171), multiple sleep disorders (AOR = 2.338), insomnia (AOR = 1.942), bone (AOR = 6.535), gastrointestinal (AOR = 4.307), genitourinary (AOR = 2.586), hematological (AOR = 4.739), or an unlisted cancer (AOR = 3.470), received hormone therapy only (AOR = 3.054), drink heavily (AOR = 2.748), or had mild insomnia (AOR = 1.828). Older participants (AOR=.972) and those with sleep apnea were less likely to use cannabis for sleep (AOR=.560). CONCLUSION: Given its prevalence, research is needed to understand how factors associated with cannabis use as a sleep aid among Canadian cancer survivors may influence its use and effectiveness and whether these factors are barriers to accessing evidence-based treatments.

Understanding the Gap: A Cross-Sectional Survey of ELSI Scholars' Dissemination Practices and Translation Goals.

BACKGROUND: Researchers engaged in the study of the ethical, legal, and social implications (ELSI) of genetics and genomics are often publicly funded and intend their work to be in the public interest. These features of U.S. ELSI research create an imperative for these scholars to demonstrate the public utility of their work and the expectation that they engage in research that has potential to inform policy or practice outcomes. In support of the fulfillment of this "translational mandate," the Center for ELSI Resources and Analysis (CERA), funded by the National Human Genome Research Institute (NHGRI), aims to facilitate community-informed, ELSI research results synthesis and dissemination. However, little is known about how ELSI research scholars define the goals of translation and imagine the intended users of their research findings. METHODOLOGY: We distributed a Qualtrics survey to ELSI scholars that aimed to determine: (1) researchers' expectations for their research findings in relation to policy or practice outcomes, (2) the stakeholder groups researchers believe could benefit from their research findings, and (3) the methods researchers use to foster the uptake of their findings by those stakeholders. RESULTS: Most ELSI researchers surveyed thought there were stakeholders that could benefit from their research findings, including health care professionals, at-risk individuals, patients, and their family members, policy-makers, and researchers/scientists, and expected their research findings to inform the creation or revision of laws, policies, or practice guidelines. Most researchers planned to disseminate findings directly to relevant stakeholders, with fewer expecting dissemination support from research funders, universities, or other entities. CONCLUSION: The broad range of research topics, disciplines, and set of potential end users represented in ELSI reseach complicate the work of a knowledge broker. Nonetheless, the CERA can play an important role in disseminating ELSI results to relevant stakeholders. Further research should explore outreach mechanisms.

How are people coping with working from home during the COVID-19 pandemic?: Experiences from the Netherlands and South Korea.

COVID-19 has made working from home routine for many. People who have had to maintain their productivity, particularly in physically and/or socially unacceptable home-working situations, experienced one of the pandemic's disadvantages. The experience can vary substantially among individuals as well as by country. This study presents the results of a comparative study of the Netherlands and Korea. Working from home was not uncommon in the Netherlands before the pandemic; however, in Korea, employers adopted working from home from its start, and that increased rapidly. An online survey enabled us to compare the physical and social conditions of current home workspaces in both countries, to understand how well-equipped they were to support people who had to work from home. We studied the changes in productivity and physical/mental health before and during COVID-19, to learn how people coped with working from home in both countries. Contrary to expectations, Koreans showed better scores than people in the Netherlands, in terms of changes in health and productivity. This article discusses various aspects of that result, such as satisfaction with home workspace, housing type, job position and prior experience, compulsoriness, and frequency of working from home. Relieving stress and concentration appeared to be the most important dimensions of telecommuters' satisfaction with working from home environments in both countries. The results are the basis for suggesting the development of strategies for a desirable WFH environment, considering different background contexts, experiences and cultures.

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of Histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch.

During tumor development, promoter CpG islands (CGIs) that are normally silenced by Polycomb repressive complexes (PRCs) become DNA hypermethylated. The molecular mechanism by which de novo DNA methyltransferase(s) catalyze CpG methylation at PRC-regulated regions remains unclear. Here we report a cryo-EM structure of the DNMT3A long isoform (DNMT3A1) N-terminal region in complex with a nucleosome carrying PRC1-mediated histone H2A lysine 119 monoubiquitination (H2AK119Ub). We identify regions within the DNMT3A1 N-terminus that bind H2AK119Ub and the nucleosome acidic patch. This bidentate interaction is required for effective DNMT3A1 engagement with H2AK119Ub-modified chromatin in cells. Furthermore, aberrant redistribution of DNMT3A1 to Polycomb target genes inhibits their transcriptional activation during cell differentiation and recapitulates the cancer-associated DNA hypermethylation signature. This effect is rescued by disruption of the DNMT3A1-acidic patch interaction. Together, our analyses reveal a binding interface critical for countering promoter CGI DNA hypermethylation, a major molecular hallmark of cancer.

Efficacy and Safety of Cell-based Immunotherapy in The Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma - A Systematic Review and Meta-analysis.

BACKGROUND: Recurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective. METHODS: We systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias. RESULTS: We screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %-29 %), median PFS of 2.37 months (95 %CI = 1.23-3.51) and median OS of 10.16 months (95 %CI = 0.67-19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %-93 %), SD rate was 22 % (95 %CI = 2 %-75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %-98 %), SD rate of 11 % (95 % CI = 0 %-82 %) and incidence rate of any grade adverse events of 29 % was achieved. CONCLUSION: CBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.

Improving care in lung cancer surgery: a review of quality measures and evolving standards.

PURPOSE OF REVIEW: Lung cancer is the leading cause of cancer-related death in the United States. Pulmonary resection, in addition to perioperative systemic therapies, is a cornerstone of treatment for operable patients with early-stage and locoregional disease. In recent years, increased emphasis has been placed on surgical quality metrics: specific and evidence-based structural, process, and outcome measures that aim to decrease variation in lung cancer care and improve long term outcomes. These metrics can be divided into potential areas of intervention or improvement in the preoperative, intraoperative, and postoperative phases of care and form the basis of guidelines issued by organizations including the National Cancer Center Network (NCCN) and Society of Thoracic Surgeons (STS). This review focuses on established quality metrics associated with lung cancer surgery with an emphasis on the most recent research and guidelines. RECENT FINDINGS: Over the past 18 months, quality metrics across the peri-operative care period were explored, including optimal invasive mediastinal staging preoperatively, the extent of intraoperative lymphadenectomy, surgical approaches related to minimally invasive resection, and enhanced recovery pathways that facilitate early discharge following pulmonary resection. SUMMARY: Quality metrics in lung cancer surgery is an exciting and important area of research. Adherence to quality metrics has been shown to improve overall survival and guidelines supporting their use allows targeted quality improvement efforts at a local level to facilitate more consistent, less variable oncologic outcomes across centers.

Early change in fatigue, insomnia, and cognitive impairment and symptom severity 3 years post-treatment in breast cancer survivors.

PURPOSE: Breast cancer is the most common form of cancer among Canadian women. Survivorship challenges include fatigue, sleep disturbance, and cognitive impairment. This study examined (1) symptom trajectory from diagnosis to 3 years; (2) whether symptom change in the first 4 months was associated with prolonged difficulties after 3 years; and (3) which factors were associated with deterioration in symptoms during the first 4 months. METHODS: This prospective observational cohort study examined 53 women (Mage = 58.6, 96.2% White, 67.9% stage I) with newly diagnosed breast cancer over 3 years. Women completed assessments before starting treatment, 4 months, and 3 years after diagnosis. Three-way repeated-measures ANOVAs evaluated symptom trajectories. A repeated-measures mediation analysis was performed to determine if change from pre-treatment to 4 months accounted for change from pre-treatment to 3 years. A series of between-subjects ANOVAs were used to determine what variables significantly differed by deterioration status. RESULTS: Perceived cognitive impairment and fatigue increased linearly from diagnosis to 3 years. Change in fatigue in the first 4 months fully accounted for its change over 3 years. Insomnia severity and sleep quality deteriorated from diagnosis to 4 months, but returned to pre-treatment levels at 3 years. Those whose fatigue and cognitive ability deteriorated during the first 4 months were younger. CONCLUSION: Efforts to identify those who are at risk of experiencing fatigue, sleep disturbance, and cognitive impairment; monitor patients early after receiving a diagnosis; and provide targeted interventions may prevent long-term deterioration and improve well-being.

Relationship Between Oral Health and Glaucoma Traits in the United Kingdom.

PRCIS: In this cross-sectional analysis of UK Biobank participants, we find no adverse association between self-reported oral health conditions and either glaucoma or elevated intraocular pressures. PURPOSE: Poor oral health may cause inflammation, which accelerates the progression of neurodegenerative diseases. We investigated the relationship between oral health and glaucoma. PATIENTS: United Kingdom Biobank participants. METHODS: This is a cross-sectional analysis of participants categorized by self-reported oral health status. Multivariable linear and logistic regression models were used. Primary analysis examined the association with glaucoma prevalence. Secondary analyses examined associations with IOP, macular retinal nerve fiber layer (mRNFL), and ganglion cell inner plexiform layer (mGCIPL) thicknesses, and interaction terms with multitrait glaucoma polygenic risk scores (MTAG PRS) or intraocular pressure (IOP) PRS. RESULTS: A total of 170,815 participants (34.3%) reported current oral health problems, including painful or bleeding gums, toothache, loose teeth, and/or denture wear. A In all, 33,059, 33,004, 14,652, and 14,613 participants were available for analysis of glaucoma, IOP, mRNFL, and mGCIPL, respectively. No association between oral health and glaucoma was identified [odds ratio (OR): 1.04, 95% CI: 0.95-1.14]. IOPs were slightly lower among those with oral disease (-0.08 mm Hg, 95% CI: -0.15, -0.009); specifically, among those with loose teeth ( P =0.03) and denture-wearers ( P <0.0001). mRNFL measurements were lower among those with oral health conditions (-0.14 µm, 95% CI: -0.27, -0.0009), but mGCIPL measurements ( P =0.96) were not significantly different. A PRS for IOP or glaucoma did not modify relations between oral health and IOP or glaucoma ( P for interactions ≥​​​​0.17). CONCLUSIONS: Self-reported oral health was not associated with elevated IOP or an increased risk of glaucoma. Future studies should confirm the null association between clinically diagnosed oral health conditions and glaucoma.

Infertility treatment is associated with increased risk of postpartum hospitalization due to heart disease.

BACKGROUND: Cardiovascular disease is a major cause of maternal mortality, but the extent to which infertility treatment is implicated in heart disease remains unclear. OBJECTIVE: To evaluate the association between infertility treatment and postpartum heart disease. METHODS: We designed a retrospective cohort study of patients who delivered in the United States between 2010 and 2018. The primary outcome was hospitalization within 12-month post-delivery due to heart disease (including ischemic heart disease, atherosclerotic heart disease, cardiomyopathy, hypertensive disease, heart failure, and cardiac dysrhythmias). We estimated the rate difference (RD) of hospitalizations among patients who conceived with infertility treatment and those who conceived spontaneously. Associations were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs), derived from Cox proportional hazards regression after adjustment for potential confounders. RESULTS: Infertility treatment was recorded in 0.9% (n = 287,813) of 31,339,991 deliveries. Rates of heart disease hospitalizations with infertility treatment and with spontaneous conception were 550 and 355 per 100,000, respectively (RD 195, 95% CI: 143-247; adjusted HR 1.99, 95% CI: 1.80-2.20). The most important increase in risk was observed for hypertensive disease (adjusted HR 2.16, 95% CI: 1.92-2.42). This increased risk was apparent as early as 30-day post-delivery (HR 1.61, 95% CI: 1.39-1.86), with progressively increasing risk up to a year. CONCLUSIONS: Although the absolute risk of postpartum heart disease hospitalization is low, infertility treatment is associated with an increased risk, especially for hypertensive disease. These findings highlight the importance of timely postpartum follow-ups in patients who received infertility treatment.

Pregnancy-associated mortality due to cardiovascular disease: Impact of hypertensive disorders of pregnancy.

BACKGROUND: Reported rates of maternal mortality in the United States have been staggeringly high and increasing, and cardiovascular disease (CVD) is a chief contributor to such deaths. However, the impact of hypertensive disorders of pregnancy (HDP) on the short-term risk of cardiovascular death is not well understood. OBJECTIVES: To evaluate the association between HDP (chronic hypertension, gestational hypertension, preeclampsia, eclampsia, and superimposed preeclampsia) and pregnancy-associated mortality rates (PMR) from all causes, CVD-related causes both at delivery and within 1 year following delivery. METHODS: We used the Nationwide Readmissions Database (2010-2018) to examine PMRs for females 15-54 years old. International Classification of Disease 9 and 10 diagnosis codes were used to identify pregnancy-associated deaths due to HDP and CVD. Discrete-time Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for mortality at delivery (0 days) and at <30, <60, <90, <180, and <365 days after delivery in relation to HDP. RESULTS: Of 33,417,736 hospital deliveries, the rate of HDP was 11.0% (n = 3,688,967), and the PMR from CVD was 6.4 per 100,000 delivery hospitalisations (n = 2141). Compared with normotensive patients, HRs for CVD-related PMRs increased with HDP severity, reaching over 58-fold for eclampsia patients. HRs were higher for stroke-related (1.2 to 170.9) than heart disease (HD)-related (0.99 to 39.8) mortality across all HDPs. Except for gestational hypertension, the increased risks of CVD mortality were evident at delivery and persisted 1 year postpartum for all HDPs. CONCLUSIONS: HDPs are strong risk factors for pregnancy-associated mortality due to CVD at delivery and within 1 year postpartum; the risks are stronger for stroke than HD-related PMR. While absolute PMRs are low, this study supports the importance of extending postpartum care beyond the traditional 42-day postpartum visit for people whose pregnancies are complicated by hypertension.

Characterizing Indicators of Engagement in HIV-Associated Healthcare and Clinical Outcomes among People with HIV and Mpox in Washington, DC: A Nested Case-Control Study of the DC Cohort.

The high proportion of people with HIV (PWH) in the 2022-2023 mpox outbreak has raised questions surrounding the association between HIV and mpox. The objectives of this study were to evaluate the association between engagement in HIV-associated healthcare and mpox diagnosis, as well as to characterize cases of mpox among PWH. The DC Cohort is a longitudinal cohort of PWH in Washington, DC. We conducted a 5:1 (controls:cases) nested case-cohort study on male participants, matching age and care site. Cases were participants with an identified mpox diagnosis. Conditional logistic regression was used to assess the impact of indicators of engagement in HIV-associated healthcare on mpox diagnosis. We identified 70 cases of mpox in DC Cohort participants randomly matched to 323 controls, for a total of 393 participants included in the analysis. Study participants were primarily non-Hispanic Black (72.3%) with a median age of 41 (IQR: 36, 50). There was no association between engagement in care and mpox diagnosis; however, low CD4 was associated with increased odds of mpox diagnosis (aOR: 4.60 (95% CI: 1.23, 17.11)). Among a cohort of PWH, engagement in care was not associated with mpox diagnosis, suggesting that the overrepresentation of PWH among mpox cases is not due to surveillance bias.

Abnormal Uterine Bleeding Associated With Hormonal Contraception.

Abnormal uterine bleeding is a common and bothersome symptom in people using hormonal contraception, and it can lead to discontinuation of reliable methods of contraception and unintended pregnancies. Clinicians should counsel individuals about the potential for abnormal bleeding at initiation of the contraceptive method. After considering and excluding other potential causes of abnormal uterine bleeding, clinicians can offer treatment options specific to each hormonal contraceptive method. This article includes algorithms to help clinicians treat abnormal uterine bleeding in people using levonorgestrel intrauterine devices, depo-medroxyprogesterone acetate, progestin implant, progestin-only pills, and combined hormonal contraception. For patients with levonorgestrel intrauterine devices, physicians should first ensure that the device is correctly placed within the uterus, then consider nonsteroidal anti-inflammatory drugs as a first-line treatment for abnormal uterine bleeding; estradiol can be used if nonsteroidal anti-inflammatory drugs are ineffective. For depo-medroxyprogesterone acetate or progestin implant users, combined oral contraceptives or nonsteroidal anti-inflammatory drugs may be considered. For patients using norethindrone progestin-only pills, changing to drospirenone progesterone-only pills may help reduce the bleeding. In people using combined hormonal contraception, it may be helpful to increase estrogen content from 20 mcg to 35 mcg per day, decrease the hormone-free interval (from seven to four or five days) in people using cyclic contraception, or start a trial of low-dose doxycycline. For continuous combined contraception users, adding a hormone-free interval of four or five days can help regulate bleeding patterns.

Impact of COVID-19 on access to and delivery of sexual and reproductive healthcare services in countries with universal healthcare systems: A systematic review.

OBJECTIVES: The COVID-19 pandemic has caused unforeseen impacts on sexual and reproductive healthcare (SRH) services worldwide, and the nature and prevalence of these changes have not been extensively synthesized. We sought to synthesise reported outcomes on the impact of COVID-19 on SRH access and delivery in comparable countries with universal healthcare systems. METHODS: Following PRISMA guidelines, we searched MEDLINE, Embase, PsycInfo, and CINAHL from January 1st, 2020 to June 6th, 2023. Original research was eligible for inclusion if the study reported on COVID-19 and SRH access and/or delivery. Twenty-eight OECD countries with comparable economies and universal healthcare systems were included. We extracted study characteristics, participant characteristics, study design, and outcome variables. The methodological quality of each article was assessed using the Quality Assessment with Diverse Studies (QuADS) tool. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed for reporting the results. This study was registered on PROSPERO (#CRD42021245596). SYNTHESIS: Eighty-two studies met inclusion criteria. Findings were qualitatively synthesised into the domains of: antepartum care, intrapartum care, postpartum care, assisted reproductive technologies, abortion access, gynaecological care, sexual health services, and HIV care. Research was concentrated in relatively few countries. Access and delivery were negatively impacted by a variety of factors, including service disruptions, unclear communication regarding policy decisions, decreased timeliness of care, and fear of COVID-19 exposure. Across outpatient services, providers favoured models of care that avoided in-person appointments. Hospitals prioritized models of care that reduced time and number of people in hospital and aerosol-generating environments. CONCLUSIONS: Overall, studies demonstrated reduced access and delivery across most domains of SRH services during COVID-19. Variations in service restrictions and accommodations were heterogeneous within countries and between institutions. Future work should examine long-term impacts of COVID-19, underserved populations, and underrepresented countries.

Placental Abruption and Cardiovascular Event Risk (PACER): Design, data linkage, and preliminary findings.

BACKGROUND: Obstetrical complications impact the health of mothers and offspring along the life course, resulting in an increased burden of chronic diseases. One specific complication is abruption, a life-threatening condition with consequences for cardiovascular health that remains poorly studied. OBJECTIVES: To describe the design and data linkage algorithms for the Placental Abruption and Cardiovascular Event Risk (PACER) cohort. POPULATION: All subjects who delivered in New Jersey, USA, between 1993 and 2020. DESIGN: Retrospective, population-based, birth cohort study. METHODS: We linked the vital records data of foetal deaths and live births to delivery and all subsequent hospitalisations along the life course for birthing persons and newborns. The linkage was based on a probabilistic record-matching algorithm. PRELIMINARY RESULTS: Over the 28 years of follow-up, we identified 1,877,824 birthing persons with 3,093,241 deliveries (1.1%, n = 33,058 abruption prevalence). The linkage rates for live births-hospitalisations and foetal deaths-hospitalisations were 92.4% (n = 2,842,012) and 70.7% (n = 13,796), respectively, for the maternal cohort. The corresponding linkage rate for the live births-hospitalisations for the offspring cohort was 70.3% (n = 2,160,736). The median (interquartile range) follow-up for the maternal and offspring cohorts was 15.4 (8.1, 22.4) and 14.4 (7.4, 21.0) years, respectively. We will undertake multiple imputations for missing data and develop inverse probability weights to account for selection bias owing to unlinked records. CONCLUSIONS: Pregnancy offers a unique window to study chronic diseases along the life course and efforts to identify the aetiology of abruption may provide important insights into the causes of future CVD. This project presents an unprecedented opportunity to understand how abruption may predispose women and their offspring to develop CVD complications and chronic conditions later in life.

Believing is seeing - the deceptive influence of bias in quantitative microscopy.

The visual allure of microscopy makes it an intuitively powerful research tool. Intuition, however, can easily obscure or distort the reality of the information contained in an image. Common cognitive biases, combined with institutional pressures that reward positive research results, can quickly skew a microscopy project towards upholding, rather than rigorously challenging, a hypothesis. The impact of these biases on a variety of research topics is well known. What might be less appreciated are the many forms in which bias can permeate a microscopy experiment. Even well-intentioned researchers are susceptible to bias, which must therefore be actively recognized to be mitigated. Importantly, although image quantification has increasingly become an expectation, ostensibly to confront subtle biases, it is not a guarantee against bias and cannot alone shield an experiment from cognitive distortions. Here, we provide illustrative examples of the insidiously pervasive nature of bias in microscopy experiments - from initial experimental design to image acquisition, analysis and data interpretation. We then provide suggestions that can serve as guard rails against bias.

Descriptive analysis of targeted carbapenemase genes and antibiotic susceptibility profiles among carbapenem-resistant Acinetobacter baumannii tested in the Antimicrobial Resistance Laboratory Network-United States, 2017-2020.

Acinetobacter baumannii is a Gram-negative bacillus that can cause severe and difficult-to-treat healthcare-associated infections. A. baumannii can harbor mobile genetic elements carrying genes that produce carbapenemase enzymes, further limiting therapeutic options for infections. In the United States, the Antimicrobial Resistance Laboratory Network (AR Lab Network) conducts sentinel surveillance of carbapenem-resistant Acinetobacter baumannii (CRAB). Participating clinical laboratories sent CRAB isolates to the AR Lab Network for characterization, including antimicrobial susceptibility testing and molecular detection of class A (Klebsiella pneumoniae carbapenemase), class B (Active-on-Imipenem, New Delhi metallo-ß-lactamase, and Verona integron-encoded metallo-ß-lactamase), and class D (Oxacillinase, blaOXA-23-like, blaOXA-24/40-like, blaOXA-48-like, and blaOXA-58-like) carbapenemase genes. During 2017‒2020, 6,026 CRAB isolates from 45 states were tested for targeted carbapenemase genes; 1% (64 of 5,481) of CRAB tested for targeted class A and class B genes were positive, but 83% (3,351 of 4,041) of CRAB tested for targeted class D genes were positive. The number of CRAB isolates carrying a class A or B gene increased from 2 of 312 (<1%) tested in 2017 to 26 of 1,708 (2%) tested in 2020. Eighty-three percent (2,355 of 2,846) of CRAB with at least one of the targeted carbapenemase genes and 54% (271 of 500) of CRAB without were categorized as extensively drug resistant; 95% (42 of 44) of isolates carrying more than one targeted gene had difficult-to-treat susceptibility profiles. CRAB isolates carrying targeted carbapenemase genes present an emerging public health threat in the United States, and their rapid detection is crucial to improving patient safety.IMPORTANCEThe Centers for Disease Control and Prevention has classified CRAB as an urgent public health threat. In this paper, we used a collection of >6,000 contemporary clinical isolates to evaluate the phenotypic and genotypic properties of CRAB detected in the United States. We describe the frequency of specific carbapenemase genes detected, antimicrobial susceptibility profiles, and the distribution of CRAB isolates categorized as multidrug resistant, extensively drug-resistant, or difficult to treat. We further discuss the proportion of isolates showing susceptibility to Food and Drug Administration-approved agents. Of note, 84% of CRAB tested harbored at least one class A, B, or D carbapenemase genes targeted for detection and 83% of these carbapenemase gene-positive CRAB were categorized as extensively drug resistant. Fifty-four percent of CRAB isolates without any of these carbapenemase genes detected were still extensively drug-resistant, indicating that infections caused by CRAB are highly resistant and pose a significant risk to patient safety regardless of the presence of one of these carbapenemase genes.