Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19.

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.

Identifying cardiovascular severe maternal morbidity in epidemiologic studies.

BACKGROUND: Cardiovascular severe maternal morbidity (CSMM) is rising and has become the leading cause of maternal mortality. Research using administrative data sets may allow for better understanding of this critical group of diseases. OBJECTIVE: To validate a composite variable of CSMM for use in epidemiologic studies. METHODS: We analysed delivery hospitalisations at an obstetric teaching hospital from 2007 to 2017. We utilised a subset of indicators developed by the Centers for Disease Control and Prevention based on ICD codes to form the composite variable for CSMM. Two expert clinicians manually reviewed all qualifying events using a standardised tool to determine whether these represented true CSMM events. Additionally, we estimated the number of CSMM cases among delivery hospitalisations without qualifying ICD codes by manually reviewing all hospitalisations with severe preeclampsia, a population at high risk of CSMM, and a random sample of 1000 hospitalisations without severe preeclampsia. We estimated validity of the composite variable. RESULTS: Among 91 355 admissions for delivery, we captured 113 potential CSMM cases using qualifying ICD codes. Of these, 65 (57.5%) were true CSMM cases. Indicators for acute myocardial infarction, cardiac arrest, and cardioversion had the highest true-positive rates (100% for all). We found an additional 70 CSMM cases in the 2102 admissions with severe preeclampsia and a single CSMM case in the random sample. Assuming a rate of 1 CSMM case per 1000 deliveries in the remaining cohort, the composite variable had a positive predictive value of 57.5% (95% CI 47,9, 66.8), a negative predictive value of 99.8% (95% CI 99.8, 99.9), a sensitivity of 29.0% (95% CI 23.2, 35.4), and a specificity of 100% (95% CI 99.9, 100.0). CONCLUSION: A novel composite variable for CSMM had reasonable PPV but limited sensitivity. This composite variable may enable epidemiologic studies geared towards reducing maternal morbidity and mortality.

Extragenital Infections Caused by Chlamydia trachomatis and Neisseria gonorrhoeae: A Review of the Literature.

In the United States, sexually transmitted diseases due to Chlamydia trachomatis and Neisseria gonorrhoeae continue to be a major public health burden. Screening of extragenital sites including the oropharynx and rectum is an emerging practice based on recent studies highlighting the prevalence of infection at these sites. We reviewed studies reporting the prevalence of extragenital infections in women, men who have sex with men (MSM), and men who have sex only with women (MSW), including distribution by anatomical site. Among women, prevalence was found to be 0.6-35.8% for rectal gonorrhea (median reported prevalence 1.9%), 0-29.6% for pharyngeal gonorrhea (median 2.1%), 2.0-77.3% for rectal chlamydia (median 8.7%), and 0.2-3.2% for pharyngeal chlamydia (median 1.7%). Among MSM, prevalence was found to be 0.2-24.0% for rectal gonorrhea (median 5.9%), 0.5-16.5% for pharyngeal gonorrhea (median 4.6%), 2.1-23.0% for rectal chlamydia (median 8.9%), and 0-3.6% for pharyngeal chlamydia (median 1.7%). Among MSW, the prevalence was found to be 0-5.7% for rectal gonorrhea (median 3.4%), 0.4-15.5% for pharyngeal gonorrhea (median 2.2%), 0-11.8% for rectal chlamydia (median 7.7%), and 0-22.0% for pharyngeal chlamydia (median 1.6%). Extragenital infections are often asymptomatic and found in the absence of reported risk behaviors, such as receptive anal and oral intercourse. We discuss current clinical recommendations and future directions for research.

Association Between Hispanic Ethnicity and Engagement in a Remote Postpartum Blood Pressure Monitoring Programs: Secondary Analysis of a Pilot Randomized Trial.

OBJECTIVE: Remote self-measured blood pressure (SMBP) programs improve racial health equity among postpartum people with hypertensive disorders of pregnancy (HDP) who receive recommended blood pressure ascertainment after hospital discharge.1-3 However, as prior studies have been conducted within racially diverse but ethnically homogeneous populations,1-3 the effect of SMBP programs on ethnicity-based inequities is less understood.4 We examined whether SMBP rates differed among Hispanic versus non-Hispanic participants in remote SMBP programs. STUDY DESIGN: This is a planned secondary analysis of a RCT conducted among postpartum patients with HDP who were enrolled into our remote SMBP program, in which they obtain SMBP and then manually enter the SMBP value into a patient portal for individual provider response. In the parent trial, consenting patients were randomized to continued manual blood pressure entry of SMBP or use of a Bluetooth-enabled blood pressure cuff synched to a smartphone application utilizing artificial intelligence to respond to each obtained blood pressure or symptom for six weeks and to flag abnormalities for providers. Both SMBP programs were available in Spanish and English. For this study, women who self-reported their ethnicity were stratified into two ethnic groups - Hispanic and non-Hispanic - regardless of randomization group. Those who did not self-report ethnicity but completed all study procedures in Spanish were also categorized as Hispanic. Outcomes were the same in the parent study and this secondary analysis. The primary outcome was ≥1 SMBP assessment within 10 days postpartum. Secondary outcomes included number of blood pressure assessments and healthcare utilization outcomes (remote antihypertensive medication initiation or dose-increase and presentation to the Emergency Department or readmission for hypertension within 30 days of discharge). Participants rated their experience with SMBP via a scale from 0 (worst possible) to 10 (best possible) and the Decision Regret Scale, which assessed their regret in SMBP program participation (0=no regret; 100=high regret)).5 Outcomes were compared between groups. Risk differences (RD) were calculated for categorical and regression coefficients for continuous outcomes. The parent RCT was IRB-approved and published on clinicaltrials.gov (NCT05595629) before enrollment. RESULTS: Among 119 women in the parent study, 83 (70%) self-reported ethnicity and the proportion of Hispanic people was similar in both treatment groups. This study compared 23 Hispanic (19% monolingual in Spanish) to 62 non-Hispanic women. Rates of SMBP assessment within 10 days postpartum was similar (Hispanic 64% vs non-Hispanic 79%; RD -0.1 (95% Confidence Interval (CI) -0.4, 0.1). There were no differences in mean number of remote SMBP assessments or rates of remote antihypertensive medication initiation or dose titration. The rates of hypertension-related presentations to the Emergency Department or hospital readmission were also similar between groups. Lastly, regardless of ethnicity, participants had low scores on the Decision Regret Scale and rated their experience with their remote SMBP program highly favorably. (See Table 1.) Conclusion: Hispanic and non-Hispanic postpartum patients with HDP had similar outcomes and favorable patient perceptions. The small sample size in this study may have produced inadequate power to detect a difference between study groups, thereby leading to Type II error. Thus, more research on Hispanic participants in remote SMBP programs is needed. However, the effect of remote SMBP programs on perinatal equity may not be limited to race-based disparities.

Characteristics of acute sexual assault care in New England emergency departments.

Objective: Interventions such as written protocols and sexual assault nurse examiner programs improve outcomes for patients who have experienced acute sexual assault. How widely and in what ways such interventions have been implemented is largely unknown. We sought to characterize the current state of acute sexual assault care in New England. Methods: We conducted a cross-sectional survey of individuals acute with knowledge of emergency department (ED) operations in relation to sexual assault care at New England adult EDs. Our primary outcomes included the availability and coverage of dedicated and non-dedicated sexual assault forensic examiners in EDs. Secondary outcomes included frequency of and reasons for patient transfer; treatment before transfer; availability of written sexual assault protocols; characteristics and scope of practice of dedicated and non-dedicated sexual assault forensic examiners (SAFEs), provision of care in SAFEs' absence; availability, coverage, and characteristics of victim advocacy and follow-up resources; and barriers to and facilitators of care. Results: We approached all 186 distinct adult EDs in New England to recruit participants; 92 (49.5%) individuals participated, most commonly physician medical directors (n = 34, 44.1%). Two thirds of participants reported they at times have access to a dedicated (n = 52, 65%, 95% confidence interval [CI], 54.5%-75.5%) or non-dedicated (n = 50, 64.1%; 95% CI, 53.5%-74.7%) SAFE, but fewer reported always having this access (n = 9, 17.3%; 95% CI, 7%-27.6%; n = 13, 26%; 95% CI, 13.8%-38.2%). We describe in detail findings related to our secondary outcomes. Conclusions: Although SAFEs are recognized as a strategy to provide high-quality acute sexual assault care, their availability and coverage is limited.

Testing and treatment after non-occupational exposures to STDs and HIV.

Sexual exposure to STDs including HIV and hepatitis is common. Sexual assault is also prevalent and should be screened for in a patient presenting for medical care after potential sexual exposure to STDs. Primary care providers should be familiar with current recommendations for STD prophylaxis and treatment after sexual exposure to STDs, and be aware that HIV postexposure prophylaxis is effective and available if indicated after sexual exposure to HIV. Providers should also be aware of the need for prompt referal for evaluation and medical care of the adult patient after a sexual assault.

A presentation of adenovirus with hypokalemia and rhabdomyolysis in pregnancy.

Background: Adenovirus infection is usually mild in presentation. However during pregnancy, the course can be more severe. Case: A 21-year-old woman in her second pregnancy presented with abdominal pain, vomiting, and fevers at 34 weeks and 4 days of gestation. Her respiratory pathogen panel on nasopharyngeal secretions was positive for adenovirus. Electrolytes were notable for hypomagnesaemia and persistent hypokalemia (nadir of 2.6 mmol/L) despite repletion but otherwise unremarkable. During her course, she developed rhabdomyolysis. During routine fetal monitoring at 35 weeks and 6 days of gestation, prolonged fetal bradycardia was identified, and an emergency caesarean delivery was performed. The infant had no clinical or laboratory evidence of adenovirus infection. The patient had a protracted clinical course but recovered with supportive care. Conclusion: Adenovirus can present with severe complications in a pregnant woman including hypokalemia and rhabdomyolysis. The mainstay of treatment is supportive care and monitoring of electrolyte abnormalities and renal function.

Surveillance of SARS-CoV-2 Antibodies in Early 2020 among Rhode Island Pregnancies.

OBJECTIVE: Limited data are available on the performance of SARS-CoV-2 antibody assays and data collected during pregnancy vary widely. The objective of this study was to estimate the seroprevalence of antibodies against SARS-CoV-2 in pregnant individuals in Rhode Island and to evaluate whether the prevalence differed by month of collection, age, county of residence, or economic status as estimated by zip code. METHODS: Pre-pandemic (2019) and early pandemic (2020) serum samples, collected for prenatal screening between 15 and 22 weeks of gestation, were analyzed utilizing two SARS-CoV-2 immunoglobulin G (IgG) automated assays that targeted the viral nucleocapsid (anti-N) or spike (anti-S) receptor binding domain proteins. RESULTS: Among 756 pre-pandemic samples, one anti-S IgG and 13 anti-N IgG were identified. No samples were positive for both. Among 787 pandemic specimens, 16 (2.03%) were positive for both anti-N IgG and anti-S IgG. When stratified by month of collection, there was a significant increase in seropositivity rate (p=0.023). Seropositivity rates were associated with lower income levels (p=0.08) but this was not statistically significant. No trend by maternal age was found (p=0.70). CONCLUSIONS: When a positive result was defined as both anti-N IgG and anti-S IgG, false positives were unlikely. Based on this methodology, serology could be utilized to monitor infection trends during pregnancy.

Development and Internal Validation of a Risk Prediction Model for Acute Cardiovascular Morbidity in Preeclampsia.

BACKGROUND: Women with preeclampsia are at increased short-term risk of adverse cardiovascular outcomes during pregnancy and the early postpartum period. We aimed to develop and internally validate a risk assessment tool to predict acute cardiovascular morbidity in preeclampsia. METHODS: The study was conducted at an academic obstetrics hospital. Participants with preeclampsia at delivery from 2007 to 2017 were included. A model to predict acute cardiovascular morbidity at delivery and within 6 weeks after delivery was developed and evaluated. The primary composite outcome included pulmonary edema/acute heart failure, myocardial infarction, aneurysm, cardiac arrest/ventricular fibrillation, heart failure/arrest during surgery or procedure, cerebrovascular disorders, cardiogenic shock, conversion of cardiac rhythm, and difficult-to-control severe hypertension. We assessed model discrimination and calibration. We used bootstrapping for internal validation. RESULTS: A total of 4171 participants with preeclampsia were included. The final model comprised 8 variables. Predictors positively associated with acute cardiovascular morbidity (presented as odds ratio with 95% confidence interval) were: gestational age at delivery (20-36 weeks: 5.36 [3.67-7.82]; 37-38 weeks: 1.75 [1.16-2.64]), maternal age (≥ 40 years: 1.65 [1.00-2.72]; 35-39 years: 1.49 [1.07-2.09]), and previous caesarean delivery (1.47 [1.01-2.13]). The model had an area under the receiver operating characteristic curve of 0.72 (95% CI 0.69-0.74). Moreover, it was adequately calibrated and performed well on internal validation. CONCLUSIONS: This risk prediction tool identified women with preeclampsia at highest risk of acute cardiovascular morbidity. If externally validated, this tool may facilitate early interventions aimed at preventing adverse cardiovascular outcomes in pregnancy and postpartum.

Pregnancy latency after preterm premature rupture of membranes: oral versus intravenous antibiotics.

BACKGROUND: Following the destruction of pharmaceutical production facilities in Puerto Rico by Hurricane Maria in September 2017, a shortage of small-volume bags of sterile intravenous fluid for infusion led to a decreased ability to administer intravenous azithromycin and ampicillin efficiently for use in the treatment of patients with preterm premature rupture of membranes. OBJECTIVE: This study aimed to assess pregnancy latency after preterm premature rupture of membranes following treatment with oral-only antibiotics compared with treatment with intravenous antibiotics followed by oral antibiotics. STUDY DESIGN: This is a retrospective historic control study comparing women with preterm premature rupture of membranes who were initiated on a 7-day oral-only regimen of azithromycin and amoxicillin (modified regimen) during a 12-month period beginning December 2017 (during which time there was a shortage of small-volume bags of intravenous fluid) to women with preterm premature rupture of membranes who were initiated on a 2-day regimen of intravenous ampicillin and azithromycin followed by 5 days of oral amoxicillin and azithromycin (standard regimen) from December 2016 to December 2018. Women were included in the study if they were diagnosed with preterm premature rupture of membranes at <34 weeks' gestation and were started on latency antibiotics, and women were excluded from the study if they had a contraindication to expectant management, a cerclage, or suspected fetal anomalies. The primary outcome was pregnancy latency, defined as time from the first dose of antibiotics to delivery. RESULTS: The 37 women who received the modified regimen and the 79 women who received the standard regimen had similar baseline characteristics. Mean (standard deviation) gestational age at time of preterm premature rupture of membranes was similar between the modified (30.5 weeks' gestation [±3.1]) and standard regimen groups (30.2 weeks' gestation [±3.2]), and the rate of group B streptococcus rectovaginal colonization was similar for both groups (27% vs 24%; P=.95). Pregnancy latency did not differ in the modified vs standard regimen (mean difference, -0.15 days; 95% confidence interval, -4.87 to 4.58) There was no statistically significant difference in the relative risk of composite maternal infection (relative risk, 0.43; 95% confidence interval, 0.05-3.53) or composite neonatal infection (relative risk, 0.43; 95% confidence interval, 0.05-3.52). CONCLUSION: Although limited by small sample size, our study suggested that adoption of an oral-only antibiotic regimen for pregnancy latency following preterm premature rupture of membranes is worthy of further study.

Communicable diseases.

Globally, infectious diseases often disproportionately affect women, and have implications for the health of future generations. The human immunodeficiency virus (HIV), tuberculosis, malaria, and schistosomiasis are four such pathogens. Infection with these organisms has a broad impact on maternal child health in many areas of the developing world, and global initiatives to control these diseases will significantly improve the health of generations to come.