Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants <28 weeks' gestation.

BACKGROUND: Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhages (grades 3,4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Prior randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates. However, the trials may have included an insufficient number of infants at risk for intraventricular hemorrhage to be able to adequately address this question. Severe intraventricular hemorrhages occur almost exclusively in infants born <28 weeks, whereas only 7% (0%-16%) of the retreatment trials' populations were <28 weeks. OBJECTIVE: To determine if the risk of severe intraventricular hemorrhage in infants delivered <28 weeks increases when the betamethasone treatment-to-delivery interval increases beyond 9 days and to determine if betamethasone retreatment prior to delivery decreases the rate of hemorrhage. STUDY DESIGN: Observational study examining the incidence of intraventricular hemorrhage before (epoch 1) and after (epoch 2) a practice change that encouraged obstetricians to retreat pregnant women still at high risk of delivery before 28 weeks' gestation when >9 days elapsed from the first dose of betamethasone. Multivariable analyses with logistic regression using generalized estimating equations techniques were conducted to examine the rates of intraventricular hemorrhage among 410 infants <28 weeks' gestation who either delivered between 1-9 days (n=290) after the first 2-dose betamethasone course or delivered ≥10 days (and eligible for retreatment) (n=120). RESULTS: After adjusting for potential confounding variables, infants who delivered ≥10 days after a single betamethasone course had an increased risk of either severe intraventricular hemorrhage alone or the combined outcome severe intraventricular hemorrhage or death before 4 days (OR (95%CI): 2.8 (1.2, 6.6)) compared with infants who delivered between 1-9 days after betamethasone. Among the 120 infants who delivered ≥10 days after the first dose of betamethasone, 64 (53%) received a second/retreatment course of antenatal betamethasone. The severe intraventricular hemorrhage rate in infants whose mothers received a second/retreatment course of betamethasone was similar to the rate in infants who delivered within 1-9 days and significantly lower than in those who delivered ≥10 days without retreatment (OR (95%CI): 0.10 (0.02, 0.65). Following the change in guidelines, the rate of retreatment in infants who delivered ≥10 days after the first betamethasone course (and before 28 weeks) increased from epoch 1 to epoch 2 (25% to 87%, p<0.001) and the rate of severe intraventricular hemorrhage decreased from 22% to 0% (p<0.001). In contrast, the rate of severe intraventricular hemorrhage in infants who delivered 1-9 days after the initial betamethasone dose (who were not eligible for retreatment) did not change between epochs 1 and 2 (12% and 11%, respectively). CONCLUSIONS: Although betamethasone's benefits on severe intraventricular hemorrhage appear to wane after the first dose, retreatment with a second course appears to restore its beneficial effects. Encouraging earlier retreatment of women at high risk of delivery before 28 weeks was associated with a lower rate of severe intraventricular hemorrhages among infants delivering <28 weeks.

Evidence of varicella zoster virus (VZV) reactivation in children with arterial ischemic stroke: Results of the VIPS II Study.

Background: Varicella zoster virus (VZV) has been associated with focal cerebral arteriopathy (FCA) and arterial ischemic stroke (AIS) in childhood. The Vascular effects of Infection in Pediatric Stroke (VIPS) II study aimed to examine this relationship in the modern era when most children in North America and Australia receive VZV vaccination with live, attenuated virus. Methods: This 22-center prospective cohort study enrolled 205 children (28 days-18 years) with AIS (2017-2022), collected baseline [hyperacute (≤72 hours; n=194) and acute (4-6 days; n=181)] and convalescent (1-6 weeks; n=74) serum samples. Sites enrolled 95 stroke-free controls with single serum samples. A virology research laboratory measured VZV IgM and IgG titers by an in-house enzyme-linked immunosorbent assay (ELISA). Baseline IgG seropositivity indicated prior exposure (vaccination/infection) and elevated IgM titers indicated recent reactivation. Results: Median (IQR) age was 11.6 (5.5-15.6) years for cases and 11.8 (6.8-15.3) years for controls. Baseline serologies indicated prior VZV exposure in 198 cases (97%) and all controls. Parents of cases reported VZV vaccination in 160 (78%) and remote chicken pox in three (1.4%). Twenty cases (9.8%) and three controls (3.1%) had serologic evidence of recent VZV reactivation (p=0.06); all had remote VZV exposure (vaccination in 19 cases and all controls) and all were asymptomatic. Recent VZV reactivation was seen in similar proportions in arteriopathic, cardioembolic, and idiopathic stroke. Of 32 cases of FCA, 4 (12.5%) had recent VZV reactivation, versus no cases of arterial dissection (n=10) or moyamoya (n=16). Conclusions: Serologic evidence of recent VZV reactivation (≈1-6 weeks prior to stroke) was present in one in 10 cases of childhood AIS, including those without arteriopathy. Clinically silent VZV reactivation may be a childhood stroke trigger despite widespread vaccination. These cases could represent waning immunity with reactivation of either vaccine virus or wild-type virus after an unrecognized secondary VZV infection.

Evidence-based prescribing of opioids after laparotomy: A quality-improvement initiative in gynecologic oncology.

Introduction: Across specialties, surgeons over-prescribe opioids to patients after surgery. We aimed to develop and implement an evidence-based calculator to inform post-discharge opioid prescription size for gynecologic oncology patients after laparotomy. Methods: In 2021, open surgical gynecologic oncology patients were called 2-4 weeks after surgery to ask about their home opioid use. This data was used to develop a calculator for post-discharge opioid prescription size using two factors: 1) age of the patient, 2) oral morphine equivalents (OME) used by patients the day before hospital discharge. The calculator was implemented on the inpatient service from 8/21/22 and patients were contacted 2-4 weeks after surgery to again assess their opioid use at home. Results: Data from 95 surveys were used to develop the opioid prescription size calculator and are compared to 95 post-intervention surveys. There was no difference pre- to post-intervention in demographic data, surgical procedure, or immediate postoperative recovery. The median opioid prescription size decreased from 150 to 37.5 OME (p < 0.01) and self-reported use of opioids at home decreased from 22.5 to 7.5 OME (p = 0.05). The refill rate did not differ (12.6 % pre- and 11.6 % post-intervention, p = 0.82). The surplus of opioids our patients reported having at home decreased from 1264 doses of 5 mg oxycodone tabs in the pre-intervention cohort, to 490 doses in the post-intervention cohort, a 61 % reduction. Conclusions: An evidence-based approach for prescribing opioids to patients after laparotomy decreased the surplus of opioids we introduced into our patients' communities without impacting refill rates.

Prophylactic indomethacin and the risk of serious pulmonary hemorrhages in preterm infants less than 28 weeks' gestation.

OBJECTIVE: To determine if prophylactic indomethacin (PINDO) decreases serious pulmonary hemorrhages in infants <28 weeks. STUDY DESIGN: Intention-to-treat analysis of 615 consecutively admitted infants during four alternating protocol-driven epochs of PINDO or expectant patent ductus arteriosus (PDA) management. RESULTS: 41/615 (6.7%) developed serious pulmonary hemorrhage at 2 (1, 3) days (median (IQR)). In unadjusted and adjusted multivariable models, infants born in a PINDO epoch had significantly lower incidences of pulmonary hemorrhage and pulmonary hemorrhage or death before 7 days. There were less moderate/large PDA during PINDO epochs. The associations between PINDO and pulmonary hemorrhage and pulmonary hemorrhage/death were no longer significant when presence of a PDA was included in the analyses. There was no apparent association between PINDO epochs and the incidence of serious intraventricular hemorrhages. CONCLUSION: Even though PINDO no longer appears to affect the incidence of sIVH it still is associated with a lower incidence of pulmonary hemorrhage.

Exploring the relationship between language, postoperative pain, and opioid use.

BACKGROUND: Racial and ethnic disparities in pain management are well documented. Differences in pain assessment and management by language have not been studied in the postoperative setting in gynecologic surgery. OBJECTIVE: This study aimed to investigate the association between language and immediate postoperative pain management by comparing pain assessments and perioperative opioid use in non-English speakers and English speakers. STUDY DESIGN: This was a retrospective cohort study comparing perioperative outcomes between non-English-speaking patients and English-speaking patients who had undergone a gynecologic oncology open surgery between July 2012 and December 2020. The primary language was extracted from the electronic medical record. Opioid use is expressed in oral morphine equivalents. Proportions are compared using chi-square tests, and mean values are compared using 2-sample t tests. Although interpreter services are widely available in our institution, the use of interpreters for any given inpatient-provider interaction is not documented. RESULTS: Between 2012 and 2020, 1203 gynecologic oncology patients underwent open surgery, of whom 181 (15.1%) were non-English speakers and 1018 (84.9%) were English speakers. There was no difference between the 2 cohorts concerning body mass index, surgical risk score, or preoperative opioid use. Compared with the English-speaking group, the non-English-speaking group was younger (57 vs 54 years old, respectively; P<.01) and had lower rates of depression (26% vs 14%, respectively; P<.01) and chronic pain (13% vs 6%, respectively; P<.01). Although non-English-speaking patients had higher rates of hysterectomy than English-speaking patients (80% vs 72%, respectively; P=.03), there was no difference in the rates of bowel resections, adnexal surgeries, lengths of surgery, intraoperative oral morphine equivalents administered, blood loss, use of opioid-sparing modalities, lengths of hospital stay, or intensive care unit admissions. In the postoperative period, compared with English-speaking patients, non-English-speaking patients received fewer oral morphine equivalents per day (31.7 vs 43.9 oral morphine equivalents, respectively; P<.01) and had their pain assessed less frequently (7.7 vs 8.8 checks per day, respectively; P<.01) postoperatively. English-speaking patients received a median of 19.5 more units of oral morphine equivalents daily in the hospital and 205.1 more units of oral morphine equivalents at the time of discharge (P=.02 and P=.04, respectively) than non-English-speaking patients. When controlling for differences between groups and several factors that may influence oral morphine equivalent use, English-speaking patients received a median of 15.9 more units of oral morphine equivalents daily in the hospital cohort and similar oral morphine equivalents at the time of discharge compared with non-English-speaking patients. CONCLUSION: Patients who do not speak English may be at risk of undertreated pain in the immediate postoperative setting. Language barrier, frequency of pain assessments, and provider bias may perpetuate disparity in pain management. Based on this study's findings, we advocate for the use of regular verbal pain assessments with language-concordant staff or medical interpreters for all postoperative patients.

Effects of Pharmacotherapy for the Treatment of Obesity in an Urban, Safety-Net Population.

OBJECTIVE: To evaluate the effect of common weight loss pharmacotherapies among low-income, racially diverse adult patients at an urban safety-net weight management clinic. METHODS: Our retrospective review from 2015 to 2019 examined patients who took either GLP-1 analog (GL) or phentermine/topiramate (PT) for ≥90 days and patients who exclusively pursued non-pharmacologic treatment for comparison. Changes in weight, blood pressure, and hemoglobin A1c at 1-year follow-up were reported. RESULTS: We analyzed 22 GL and 26 PT patients and included 40 patients who pursued only lifestyle modifications (LM). All three groups achieved significant weight loss at one year: GL -3.69 (interquartile range (IQR): -11.0, -1.77) kg (p=0.0004), PT -7.01 (IQR: -13.4, -1.45) kg (p<0.001), and LM -3.01 (IQR: -6.81, 1.13) kg (p=0.005). There was no significant difference in the median weight loss (p=0.11) between the three groups. We observed no significant changes in systolic blood pressure but saw a significant change of -0.75 in hemoglobin A1c (IQR: -1.35, -0.25) (p=0.01) among patients with diabetes in the GL group. CONCLUSIONS: Our real-world applications of GLP-1 and phentermine/topiramate suggest that both are effective weight loss medication regimens in low-socioeconomic status patients.

Proportion of Ugandans with pre-pandemic SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell responses: A pilot study.

The estimated mortality rate of the SARS-CoV-2 pandemic varied greatly around the world. In particular, multiple countries in East, Central, and West Africa had significantly lower rates of COVID-19 related fatalities than many resource-rich nations with significantly earlier wide-spread access to life-saving vaccines. One possible reason for this lower mortality could be the presence of pre-existing cross-reactive immunological responses in these areas of the world. To explore this hypothesis, an exploratory study of stored peripheral blood mononuclear cells (PBMC) from Ugandans collected from 2015-2017 prior to the COVID-19 pandemic (n = 29) and from hospitalized Ugandan COVID-19 patients (n = 3) were examined using flow-cytometry for the presence of pre-existing SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell populations using four T-cell epitope mega pools. Of pre-pandemic participants, 89.7% (26/29) had either CD4+ or CD8+, or both, SARS-CoV-2 specific T-cell responses. Specifically, CD4+ T-cell reactivity (72.4%) and CD8+ T-cell reactivity (65.5%) were relatively similar, and 13 participants (44.8%) had both types of cross-reactive types of T-cells present. There were no significant differences in response by sex in the population, however this may be in part due to the limited sample size examined. The rates of cross-reactive T-cell populations in this exploratory Ugandan population appears higher than previous estimates from resource-rich countries like the United States (20-50% reactivity). It is unclear what role, if any, this cross-reactivity played in decreasing COVID-19 related mortality in Uganda and other African countries, but does suggest that a better understanding of global pre-existing immunological cross-reactivity could be an informative data of epidemiological intelligence moving forward.

The Impact of Patient-Physician Racial and Gender Concordance on Patient Satisfaction with Outpatient Clinic Visits.

BACKGROUND: Patient and provider race and gender concordance (patient and physician identify as the same race/ethnicity or gender) may impact patient experience and satisfaction. OBJECTIVE: We sought to examine how patient and physician racial and gender concordance effect patient satisfaction with outpatient clinical encounters. Furthermore, we examined factors that changed satisfaction among concordant and discordant dyads. DESIGN: Consumer Assessment of Healthcare Provider and Systems (CAHPS) Patient Satisfaction Survey Scores were collected from outpatient clinical encounters between January 2017 and January 2019 at the University of California, San Francisco. PARTICIPANTS: Patients who were seen in the eligible time period, who voluntarily provided physician satisfaction scores. Providers with fewer than 30 reviews and encounters with missing data were excluded. MAIN MEASURES: Primary outcome was rate of top satisfaction score. The provider score (1-10 scale) was dichotomized as "top score (9-10)" and "low scores (<9)." KEY RESULTS: A total of 77,543 evaluations met inclusion criteria. Most patients identified as White (73.5%) and female (55.4%) with a median age of 60 (IQR 45, 70). Compared to White patients, Asian patients were less likely to give a top score even when controlling for racial concordance (OR: 0.67; CI 0.63-0.714). Telehealth was associated with increased odds of a top score relative to in-person visits (OR 1.25; CI 1.07-1.48). The odds of a top score decreased by 11% in racially discordant dyads. CONCLUSIONS: Racial concordance, particularly among older, White, male patients, is a nonmodifiable predictor of patient satisfaction. Physicians of color are at a disadvantage, as they receive lower patient satisfaction scores, even in race concordant pairs, with Asian physicians seeing Asian patients receiving the lowest scores. Patient satisfaction data is likely an inappropriate means of determining physician incentives as such may perpetuate racial and gender disadvantages.

Telemedicine in an adolescent and young adult medicine clinic: a mixed methods study.

BACKGROUND: Adolescents and young adults are a diverse patient population with unique healthcare needs including sensitive and confidential services. Many clinics serving this population began offering telemedicine during the Covid-19 pandemic. Little is known regarding patient and parent experiences accessing these services via telemedicine. METHODS: To assess for trends and disparities in telemedicine utilization in the first year of the pandemic, we used the electronic health record to obtain patient demographic data from an adolescent and young adult medicine clinic in a large urban academic institution. Characteristics of patients who had accessed telemedicine were compared to those who were only seen in person. Mean age was compared using t-test, while other demographic variables were compared using chi-squared test or Fisher's exact test. We performed qualitative semi-structured interviews with patients and parents of patients in order to characterize their experiences and preferences related to accessing adolescent medicine services via telemedicine compared to in-person care. RESULTS: Patients that identified as female, white race, Hispanic/Latinx ethnicity were more likely to have utilized telemedicine. Telemedicine use was also more prevalent among patients who were privately insured and who live farther from the clinic. Although interview participants acknowledged the convenience of telemedicine and its ability to improve access to care for people with geographic or transportation barriers, many expressed preferences for in-person visits. This was based on desire for face-to-face interactions with their providers, and perception of decreased patient and parent engagement in telemedicine visits compared to in-person visits. Participants also expressed concern that telemedicine does not afford as much confidentiality for patients. CONCLUSIONS: More work is needed to address patient and parent preferences for telemedicine as an adjunct modality to in-person adolescent and young adult medicine services. Optimizing quality and access to telemedicine for this patient population can improve overall healthcare for this patient population.

The Impact of Patient Travel Distance on Outpatient Visit Satisfaction: Comparison of Telehealth and Traditional In-Person Visits.

Introduction: Patient satisfaction has been shown to changes based on the distance a patient to see their physician. We sought to examine the effects of telehealth on patient satisfaction. Methods: We examined patient satisfaction survey scores from outpatient clinics at University of California, San Francisco. Patient home and clinic addresses were used to calculate distance in kilometers (km). Outcomes were "top scores (9-10)" and "low scores (<9)." Results: Of 103,124 evaluations that met inclusion criteria, those where patient traveled >100 km for in-person visits had more top scores (84%) than those traveled <10 km (80.2%). Relative to in-person visits, telehealth was associated with an increased odds (odds ratio [OR]: 1.48) of receiving a top score at all distances. Those traveling >100 km had the highest odds of top score for telehealth (OR: 1.86). Conclusions: Patients receiving care through telehealth, particularly those far from the outpatient clinic, are more likely to provide high patient satisfaction scores for the visit provider.

More than just noise: Association of pulsatile tinnitus with anxiety, depression, and reduction of quality of life.

BACKGROUND: While many of the causes of pulsatile tinnitus (PT) are treatable with endovascular approaches, the risks of treatment must be balanced with the risks of the underlying cause and the psychological impact of symptoms on patients. While many physicians have anecdotal experience, the comorbid relationship of depression and anxiety with PT is unknown. The objectives of this study are to quantify the prevalence of depression and anxiety, and, to identify the demographic risk factors for impactful depression and anxiety in patients with PT. METHODS: Subjects recruited from online PT groups filled out secure online questionnaires that included demographic questions, validated Tinnitus Functional Index (TFI) as well as PHQ-9 and GAD-7 questionnaires to assess the prevalence of concurrent depression and anxiety, respectively. RESULTS: Sample included 515 surveys (84% female, 65% unemployed, mean(sd) age = 46.4 years (14.2)). Median symptom duration was 1.9 years. Data showed 46% and 37% of patients with moderate to severe depression and anxiety, respectively. Higher TFI scores were associated with moderate to severe depression (OR 1.07; 95% CI 1.06-1.09, p < 0.001) and anxiety (OR 1.05, 95% CI 1.04-1.06, p < 0.001), with TFI subscores also independently being associated in a univariate analysis. CONCLUSIONS: The prevalence of moderate to severe depression and anxiety in the PT population, which was previously unknown, is estimated in our study to be 46% and 37%, respectively. Significant association of TFI score with increased depression and anxiety scales adds further evidence of the impact of PT on the psychological health of these patients.

Patent ductus arteriosus (PDA) and pulmonary morbidity: can early targeted pharmacologic PDA treatment decrease the risk of bronchopulmonary dysplasia?

A persistent left-to-right shunt through a patent ductus arteriosus (PDA) increases the rate of pulmonary hydrostatic fluid filtration, impairs pulmonary mechanics, and prolongs the need for respiratory support. Infants with a moderate/large PDA shunt that persists for more than 7-14 days are at increased risk for developing bronchopulmonary dysplasia (BPD) if they also require invasive ventilation for more than 10 days. In contrast, infants who require invasive ventilation for less than 10 days have similar rates of BPD no matter how long they are exposed to a moderate/large PDA shunt. Although pharmacologic PDA closure decreases the risk of abnormal early alveolar development in preterm baboons that are ventilated for 2 weeks, the findings from recent randomized controlled trials, as well as a quality improvement project, suggest that routine early targeted pharmacologic treatments, as currently employed, do not appear to alter the incidence of BPD in human infants.

Prophylactic indomethacin, antenatal betamethasone, and the risk of intestinal perforation in infants <28 weeks' gestation.

OBJECTIVE: To determine if intestinal perforations before 14 days (either spontaneous (SIP) or necrotizing enterocolitis-induced) are increased when infants who received antenatal betamethasone shortly before birth are treated with prophylactic indomethacin (PINDO). STUDY DESIGN: Observational study of 475 infants <28 week's gestation assigned to either a PINDO-protocol (n = 231) or expectant management protocol (n = 244) during consecutive protocol epochs. RESULTS: Intestinal perforations before 14 days occurred in 33/475 (7%). In unadjusted and adjusted models, we found no associations between PINDO-protocol and intestinal perforations. PINDO-protocol did not increase intestinal perforations or SIP-alone even when given to infants who received betamethasone <7 or <2 days before delivery. 213/231 (92%) PINDO-protocol infants actually received indomethacin. The results were unchanged when examined just in those who received indomethacin. CONCLUSION: In our study, early intestinal perforations and SIP-alone were not increased when PINDO was used by protocol in infants who received antenatal betamethasone shortly before birth.

Patent ductus arteriosus and the risk of bronchopulmonary dysplasia-associated pulmonary hypertension.

BACKGROUND: The aim of the study was to determine whether prolonged exposure to a moderate/large patent ductus arteriosus left-to-right shunt (PDA) increases the risk of late (beyond 36 weeks) pulmonary hypertension (BPD-PH) and pulmonary vascular disease (BPD-PVD) during the neonatal hospitalization in preterm infants (<28 weeks' gestation) with bronchopulmonary dysplasia (BPD). METHODS: All infants requiring respiratory support ≥36 weeks had systematic echocardiographic evaluations for BPD-PH at planned intervals. Infants were classified as having either flow-associated BPD-PH (BPD-flow-PH) or BPD-PVD. RESULTS: 256 infants survived ≥36 weeks: 105 had NO BPD (were off respiratory support by 36 weeks); 151 had BPD. 22/151 had BPD-PH (12/22 had BPD-flow-PH from a PDA that persisted beyond 36 weeks; 10/22 had BPD-PVD). Moderate/large PDA shunts that persisted beyond 36 weeks were significantly associated with an increased incidence of BPD-PH due to BPD-flow-PH. We found no association between the duration of PDA exposure and the incidence of BPD-PVD. CONCLUSIONS: Moderate/large PDA shunts increase the risk of flow-associated BPD-PH when present beyond 36 weeks. Although term infants with PDA-congenital heart disease can develop pulmonary vascular remodeling and PVD after months of PDA exposure, we found no echocardiographic evidence in preterm infants that prolonged PDA exposure increases the incidence of BPD-PVD during the neonatal hospitalization. IMPACT: In our study, preterm infants (<28 weeks' gestation) with bronchopulmonary dysplasia (BPD) had a 15% incidence of pulmonary hypertension (PH) beyond 36 weeks' postmenstrual age as a comorbidity. Moderate/large patent ductus arteriosus (PDA) shunts increased the risk of flow-associated PH when present beyond 36 weeks. Although months of prolonged PDA exposure can cause pulmonary vascular remodeling and pulmonary vascular disease (PVD) in term infants with PDA-congenital heart disease, we found no echocardiographic evidence for an association between the duration of PDA exposure and the incidence of late PVD during the neonatal hospitalization in preterm infants with BPD.

High proportion of Ugandans with pre-pandemic SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell responses.

The estimated mortality rate of the SARS-CoV-2 pandemic varied greatly around the world with multiple countries in East, Central, and West Africa having significantly lower rates of COVID-19 related fatalities than many resource-rich nations with significantly earlier wide-spread access to life-saving vaccines. One possible reason for this lower mortality could be the presence of pre-existing cross-reactive immunological responses in these areas of the world. To explore this hypothesis, stored peripheral blood mononuclear cells (PBMC) from Ugandans collected from 2015-2017 prior to the COVID-19 pandemic (n=29) and from hospitalized Ugandan COVID-19 patients (n=3) were examined using flow-cytometry for the presence of pre-existing SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell populations using four T-cell epitope mega pools. Of pre-pandemic participants, 89.7% (26/29) had either CD4+ or CD8+, or both, SARS-CoV-2 specific T-cell responses. Specifically, CD4+ T-cell reactivity (72.4%) and CD8+ T-cell reactivity (65.5%) were relatively similar, and 13 participants (44.8%) had both types of cross-reactive types of T-cells present. There were no significant differences in response by sex in the population. The rates of cross-reactive T-cell populations in these Ugandans is higher than previous estimates from resource-rich countries like the United States (20-50% reactivity). It is unclear what role, if any, this cross-reactivity played in decreasing COVID-19 related mortality in Uganda and other African countries, but does suggest that a better understanding of global pre-existing immunological cross-reactivity could be an informative data of epidemiological intelligence moving forward.

Effects of prophylactic indomethacin on morbidity and mortality in infants <25 weeks' gestation: a protocol driven intention to treat analysis.

OBJECTIVE: To determine if prophylactic indomethacin (PINDO) decreases death or bronchopulmonary dysplasia-grades 2 and 3 (death/BPD) in newborns <25 weeks. STUDY DESIGN: Intention-to-treat, cohort-controlled study of 106 infants admitted during three alternating epochs of PINDO or Expectant patent ductus arteriosus (PDA) management. RESULTS: At 7-8 days 85% of Expectant Management epoch infants had a moderate/large PDA (median exposure was 23 days). Among PINDO epoch infants only 24% still had a PDA at 7-8 days. There were no significant differences in the incidence of death/BPD or of secondary outcomes (BPD, death, necrotizing enterocolitis/spontaneous perforations, or intraventricular hemorrhage (grades 3 or 4)) in either unadjusted or adjusted comparisons between infants born in a PINDO epoch and those born in the Expectant Management epoch. CONCLUSION: Despite being at high risk for PDA-related morbidities, PINDO did not appear to alter the rates of our primary and secondary outcomes in infants <25 weeks.

Hemorrhagic Stroke in Children and Adults With Sickle Cell Anemia: The Post-STOP Cohort.

BACKGROUND: Hemorrhagic stroke in young patients with sickle cell anemia remains poorly characterized. METHODS: The Post-STOP (Stroke Prevention Trial in Sickle Cell Anemia) retrospective study collected follow-up data on STOP and STOP II clinical trial cohorts. From January 2012 to May 2014, a team of analysts abstracted data from medical records of prior participants (all with sickle cell anemia). Two vascular neurologists reviewed data to confirm hemorrhagic strokes defined as spontaneous intracerebral, subarachnoid, or intraventricular hemorrhage. Incidence rates were calculated using survival analysis techniques Results: Follow-up data were collected from 2850 of 3835 STOP or STOP II participants. Patients (51% male) were a median of 19.1 (interquartile range, 16.6-22.6) years old at the time of last known status. The overall hemorrhagic stroke incidence rate was 63 per 100 000 person-years (95% CI, 45-87). Stratified by age, the incidence rate per 100 000 person-years was 50 (95% CI, 34-75) for children and 134 (95% CI, 74-243) for adults >18 years. Vascular abnormalities (moyamoya arteriopathy, aneurysm or cavernous malformation) were identified in 18 of 35 patients with hemorrhagic stroke. CONCLUSIONS: The incidence rate of hemorrhagic stroke in patients with sickle cell anemia increases with age. Structural vascular abnormalities such as moyamoya arteriopathy and aneurysms are common etiologies for hemorrhage and screening may be warranted.

Evaluation of Hidradenitis Suppurativa Diagnostic Criteria in Pediatric Patients.

Importance: Hidradenitis suppurativa (HS) is associated with considerable diagnostic delay. Although most patients report adolescent onset, existing HS diagnostic criteria may not adequately capture disease in pediatric populations. Objectives: To determine the proportion of physician-diagnosed pediatric patients with HS who met diagnostic criteria, and describe demographics, disease characteristics, and diagnostic patterns among pediatric patients with HS. Design, Setting, and Participants: In this retrospective, cross-sectional study, electronic medical records from 2 sites of a single academic tertiary care center were included. Eligible patients were those born after January 1, 1993, and assigned International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes for HS (ICD-9 705.83/ICD-10 L73.2) between January 1, 2012, and July 1, 2021. Patients were excluded if they were older than 18 years at diagnosis, had inaccessible diagnostic visit notes, or were unintentionally assigned an HS ICD code. Exposures: Pediatric patients with HS. Main Outcomes and Measures: Fulfillment of diagnostic criteria in pediatric patients with HS. Results: A total of 297 adolescents with HS were included in the study; 123 patients were female (78.1%), 78 self-identified as Black (26.3%), and 116 self-identified as Hispanic (39.1%). The median (IQR) age at diagnosis was 14.0 (13.0-16.0) years. Documentation from the diagnostic visit demonstrated that 127 (42.8%) patients did not meet all 3 major HS diagnostic criteria. Of these patients, 122 (96.1%) did not meet the recurrence interval criterion (≥2 lesions within 6 months). Overall, 96 patients who did not meet the recurrence interval criterion had documentation from additional visits in the health system; 59 (61.5%) had documentation of 1 or more additional lesions consistent with HS. Review of these additional records demonstrated that 26 of these 59 (44.1%) patients met the recurrence interval criterion after diagnosis, and 44 (74.6%) had recurrent lesions within a 1-year interval (median, 6.5 months; interquartile range, 3.5-12.2 months). Medical chart review was conducted from November 22, 2021, to January 12, 2022. Analysis was conducted from January 12, 2022, to January 15, 2022. Conclusions and Relevance: Overall, 118 (40%) of 297 pediatric patients with HS in this retrospective cross-sectional study did not meet all major diagnostic criteria at the time of diagnosis, largely due to failure to fulfill the 6-month recurrence interval criterion. Future studies are needed to determine the appropriate recurrence interval to facilitate timely diagnosis and promote clinical trial eligibility for pediatric patients with HS.