HELLP syndrome at <23 weeks' gestation: a systematic literature review.

OBJECTIVE: We performed a systematic review to evaluate the clinical presentation and maternal and fetal outcomes in pregnancies with early-onset HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. DATA SOURCES: PubMed, Ovid MEDLINE, Scopus, CINAHL, Cochrane Library, and ClinicalTrials.gov were queried from inception through January 1, 2023 with the following terms: "HELLP syndrome," "HELLP," "hemolysis, elevated liver enzymes, low platelets," "hemolysis, elevated liver enzymes, low platelets syndrome," "pre-viable," "peri-viable," "previable," "periviable," "first trimester," "second trimester," "before 23 weeks," "<23 weeks," "<23 week gestation," and "before 23 weeks gestation." We also included an additional case from our institution. STUDY ELIGIBILITY CRITERIA: Abstracts, unpublished studies, and review articles were excluded, yielding 46 studies that met our inclusion criteria. METHODS: Two reviewers (N.S.I. and M.H.M.) performed the study selection and subsequent data extraction independently, after which the results were reviewed together. PRISMA guidelines were followed, and our study was registered at PROSPERO (CRD42021292692). RESULTS: A total of 55 patients had 58 pregnancies complicated by early-onset HELLP syndrome, including 3 with recurrent HELLP. The most common presenting signs/symptoms were abdominal pain (35/45; 78%), hypertension (32/49; 65%), nausea/vomiting (16/45; 36%), headache (13/45; 29%), and edema (8/45; 18%). Lactate dehydrogenase ≥600 IU/L was observed in 21 of 31 (68%) cases, whereas liver enzyme abnormalities and thrombocytopenia were reported in 48 of 51 (94%) and 50 of 54 (93%) cases, respectively. Maternal complications were encountered in 25 of 56 (45%) cases. The most common complications were hepatic (13/56; 23%), central nervous system-related (11/56; 20%), and respiratory (11/56; 20%). In 36 of 57 (63%) cases, pregnancy was terminated. Of the 21 continued pregnancies, early fetal death (at <20 weeks' gestation) was reported in 10 (48%), stillbirth in 6 (28%), and neonatal demise in 2 (10%). Living neonates were reported in 3 of 21 (14%) cases, all delivered at 23 weeks. The perinatal mortality rate was 73% (8/11). One case (2%) reported maternal death. Antiphospholipid syndrome was diagnosed in 14 of 29 (48%) cases. CONCLUSION: Early-onset HELLP syndrome presents with symptoms similar to those observed in later gestation. Maternal complications are life-threatening, with the most common complications being hepatic, central nervous system-related, and respiratory. Fetal outcomes are poor.

Paediatric dental outcomes among children exposed to chemotherapy in utero.

AIM: Our study prospectively evaluated dental development in children exposed to chemotherapy in utero compared with unexposed controls. DESIGN: Women who received chemotherapy while pregnant were enrolled in a research registry. After age two, each child's dentist was asked to complete a questionnaire about dental abnormalities and malformations, as well as for their unexposed siblings. Multivariate linear regression adjusting for age was used to compare the groups. RESULTS: Dental information was received for 67 exposed children and 59 controls. The majority of mothers were treated for breast cancer (79.1%) and primarily received doxorubicin (89.6%) and cyclophosphamide (80.6%). Mean gestational age at first exposure was 20.7 (±5.7) weeks. Mean age at dental evaluation was 8.0 (±4.3) years for exposed and 10.4 (±5.1) years for controls (P < .01). Missing teeth, tooth size, shape, and color did not differ significantly between groups. There was no statistical difference in dental caries, facial abnormalities, or abnormalities of enamel or gingiva. There was no association between any chemotherapy agent or regimen and increased risk of dental abnormalities. CONCLUSIONS: Overall, there was no difference in dental abnormalities between groups. These negative findings may be because no one received chemotherapy prior to 14 weeks when formation of primary teeth was beginning.

Lysosomal storage disorders as an etiology of nonimmune hydrops fetalis: A systematic review.

We performed a systematic review of the literature to evaluate the incidence and types of lysosomal storage disorders (LSD) in case series of nonimmune hydrops fetalis (NIHF). PubMed, Ovid, and clinicaltrials.gov were reviewed for case series evaluating the workup of NIHF diagnosed in utero or in the neonatal period in human subjects from 1979 to August 2020. Retrospective case series with at least five cases of fetal and/or neonatal NIHF with its workup mentioned were identified. Idiopathic NIHF was defined as NIHF without an apparent cause after initial standard-of-care workup. In total, 22 case series with 2678 total cases of NIHF were identified. The overall incidence of LSD was 6.6% (177/2663) in NIHF cases that were tested for any LSD, and 8.2% (177/2151) in idiopathic NIHF cases. The most common LSD identified in cases of NIHF were mucopolysaccharidosis type VII, galactosialidosis, infantile sialic acid storage disease, Gaucher disease, GM1 gangliosidosis, and sialidosis. More than 40% of the most common LSD causes of NIHF have a potential postnatal treatment. LSD testing for NIHF allows for early diagnosis, better counseling and appropriate management, planning for possible early treatment, and counseling for recurrence risk.

Lymphedema in ovarian cancer survivors: Assessing diagnostic methods and the effects of physical activity.

BACKGROUND: Lymphedema is a poorly understood side effect of gynecologic cancer treatment. This study was designed to determine the prevalence of lower limb lymphedema (LLL) in a sample of ovarian cancer survivors via 3 different diagnostic methods and to assess the effect of a randomized exercise intervention. METHODS: Physically inactive ovarian cancer survivors (n = 95) were enrolled in a 6-month randomized trial of exercise (primarily brisk walking) versus attention control. LLL was measured at baseline and 6-month visits via a self-report questionnaire, optoelectronic perometry, and an evaluation by a certified lymphedema specialist. RESULTS: LLL prevalence ranged from 21% to 38% according to the diagnostic method, and there was substantial agreement between the self-report questionnaire and the lymphedema specialist evaluation (κ = 0.61). There was no agreement between the evaluation with optoelectronic perometry and the specialist evaluation. With LLL defined by any method, the baseline prevalence was 38% in both groups. At 6 months, both groups experienced a decreased LLL prevalence: 28% in the exercise group and 35% in the control group. There was no difference in the change in lymphedema prevalence between the 2 groups (P = .64). Body mass index was a significant predictor of LLL. CONCLUSIONS: With a potential prevalence of LLL as high as 40%, further evaluation of diagnostic methods is required to better characterize this side effect of ovarian cancer treatment. No adverse effect of exercise on LLL was found. Further research is strongly needed to evaluate predictors of LLL and the effects of exercise on LLL in order to develop effective physical activity recommendations for women with ovarian cancer. Cancer 2018;124:1929-37. © 2018 American Cancer Society.

Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis.

Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with 5-year survival rates of ∼90% even after largely eliminating cranial radiation. This meta-analysis assesses the long-term neurocognitive functioning after chemotherapy-only regimens among survivors of childhood ALL. We conducted a systematic review to identify studies that evaluated long-term neurocognitive functioning following treatment of ALL by searching MEDLINE/PubMed, Database of Abstracts of Reviews of Effects, and secondary sources. Studies were included if ALL survivors were in continuous first remission, did not receive any radiation, were at least ≥2 years off therapy or ≥5 years since diagnosis, and were compared with a healthy control group. Weighted mean differences with 95% confidence intervals (CIs) were calculated. Ten nonexperimental studies met all eligibility criteria and included 509 patients and 555 controls. Meta-analysis demonstrated statistically significant moderate impairment across multiple neurocognitive domains evaluated, with intelligence most affected. Significant differences in standard deviation (SD) scores were found for Full Scale intelligence quotient (IQ) (-0.52 SD; 95% CI, -0.68 to -0.37), Verbal IQ (-0.54 SD; 95% CI, -0.69 to -0.40), and Performance IQ (-0.41 SD; 95% CI, -0.56 to -0.27); these SD scores correspond to changes in IQ of 6 to 8 points. Working memory, information processing speed, and fine motor domains were moderately, but statistically significantly, impaired. Meta-analysis of ALL survivors treated without cranial radiation demonstrated significant impairment in IQ and other neurocognitive domains. Patients and their families should be informed about these potential negative effects to encourage surveillance and educational planning. Both preventive and intervention strategies are needed.

Experiences with the survivorship care plan in primary care providers of childhood cancer survivors: a mixed methods approach.

PURPOSE: Focusing on primary care providers (PCPs) of known childhood cancer survivors, we used a mixed methods approach to understand providers' experiences with the survivorship care plan (SCP), as well as preferences and barriers regarding survivorship care. METHODS: The SCP was sent to 202 eligible PCPs of patients attending a regional survivorship clinic. The PCPs then completed quantitative postal surveys. Sixteen PCPs underwent an additional qualitative interview. Provider characteristics were examined as potential predictors of experiences, preferences, and barriers regarding survivorship care. Grounded theory was utilized to analyze the qualitative data. RESULTS: Respondents (n=134) included 55% pediatricians, 23% internists, 20% family practitioners, and 2% obstetricians/gynecologists. Only 8% of PCPs preferred to have primary responsibility for survivorship care; 46% favored a specialized clinic. A minority of PCPs reported that they felt "very comfortable" using the SCP to guide surveillance (31%) or deliver all survivorship care (3%). Endorsed barriers included lack of knowledge/training (74%), not recalling or understanding the contents of the SCP (69%), and uncertainty about who is responsible for providing care (58%). Two distinct themes emerged from the qualitative interviews: a preference not to be responsible for survivorship care, and uncertain utility of the SCP. CONCLUSIONS: Our study suggests that PCPs of childhood cancer survivors generally felt uncomfortable using the SCP and providing survivorship care. Even with the availability of the SCP, the biggest barrier was lack of knowledge. Our data suggests that including PCPs in survivorship care will require additional educational opportunities and evaluation of more collaborative models of care delivery.

How Connecticut health directors deal with public health budget cuts at the local level.

OBJECTIVES: We investigated the perspectives of local health jurisdiction (LHJ) directors on coping mechanisms used to respond to budget reductions and constraints on their decision-making. METHODS: We conducted in-depth interviews with 17 LHJ directors. Interviews were audio recorded, transcribed, and analyzed using the constant comparative method. RESULTS: LHJ directors use a range of coping mechanisms, including identifying alternative revenue sources, adjusting services, amending staffing arrangements, appealing to local political leaders, and forming strategic partnerships. LHJs also face constraints on their decision-making because of state and local statutory requirements, political priorities, pressures from other LHJs, and LHJ structure. CONCLUSIONS: LHJs respond creatively to budget cuts to maintain important public health services. Some LHJ adjustments to administrative resources may obscure the long-term costs of public health budget cuts in such areas as staff morale and turnover. Not all coping strategies are available to each LHJ because of the contextual constraints of its locality, pointing to important policy questions on identifying optimum jurisdiction size and improving efficiency.

A qualitative evaluation of capnography use in paediatric sedation: perceptions, practice and barriers.

AIMS AND OBJECTIVES: We explored perceptions about capnography for procedural sedation and barriers to use in a paediatric emergency department. BACKGROUND: Capnography is a sensitive monitor of ventilation and is increasingly being studied in procedural sedation. While benefits have been found, it has not gained wide acceptance for monitoring of children during sedation. DESIGN: A qualitative exploratory study was performed. METHODS: Using a grounded theory approach, physicians and nurses from the paediatric emergency department participated in one-on-one interviews about their experiences with and opinions of capnography. An iterative process of data collection and analysis was used to inductively generate theories and themes until theoretical saturation was achieved. RESULTS: Five physicians and 12 nurses were interviewed. Themes included: Experiences: Participants felt that procedural sedation is safe and adverse events are rare. Normal capnography readings reassured providers about the adequacy of ventilation. Knowledge: Despite experience with capnography, knowledge and comfort varied. Most participants requested additional education and training. Diffusion of Use: While participants expressed positive opinions about capnography, use for sedation was infrequent. Many participants felt that capnography use increased in other paediatric populations, such as patients with altered mental status, ingestions or head trauma. Barriers: Identified barriers to use included a lack of comfort with or knowledge about equipment, lack of availability of the monitor and cannulas, lack of inclusion of these supplies on a checklist for procedural sedation preparedness, and lack of a policy for use of capnography during sedation. CONCLUSION: Capnography use during sedation in the paediatric emergency department is limited despite positive experiences and opinions about this device. Addressing modifiable barriers such as instrument availability, continuing education, and inclusion on a checklist may increase use of capnography during sedation. RELEVANCE TO CLINICAL PRACTICE: Despite the perceived benefits, a broad implementation plan is required to introduce capnography successfully to the paediatric emergency department.

Use of cell salvage at the time of cesarean delivery: a meta-analysis of randomized controlled trials.

OBJECTIVE: Excess blood loss from obstetrical hemorrhage requires transfusion of donor blood, a finite resource. Intraoperative cell salvage collects a patient's own blood that has been lost during cesarean delivery and returns it to their own circulation. We performed a meta-analysis to examine the perioperative outcomes in patients receiving cell salvage at the time of cesarean delivery. DATA SOURCES: Scopus, PubMed, Cochrane Central Register of Controlled Trials, Ovid Medline, and clinicaltrials.gov were searched from database inception through October 2023. STUDY ELIGIBILITY CRITERIA: Eligible studies included randomized controlled trials comparing the use of cell salvage to standard-of-care during cesarean delivery. METHODS: Two authors independently extracted data. Preferred Reporting Items of Systematic Reviews and Meta-Analysis guidelines were used for data extraction and quality assessment. The primary outcomes were the rate of donor blood transfusion and change in hemoglobin level. The secondary outcomes included transfusion reaction, amniotic fluid embolism, and length of hospital stay. Results were summarized as weighted mean difference or risk ratio with associated 95% confidence intervals. Heterogeneity was measured using Higgins I2. RESULTS: A total of 5 randomized controlled trials (n=3361) comparing cell salvage to standard care during cesarean delivery met the inclusion criteria. Primary analysis showed a significant decrease in receiving allogeneic blood transfusion with intraoperative cell salvage use vs standard care (odds ratio, 0.32; 95% confidence interval, 0.23-0.46), with no change in hemoglobin drop (mean difference, -0.77; 95% confidence interval, -1.67 to -0.14). The secondary outcomes showed no difference in transfusion reaction (odds ratio, 0.56; 95% confidence interval, 0.06-5.59), and length of hospital stay (mean difference, -1.90; 95% confidence interval, -4.85 to 1.06). No cases of amniotic fluid embolism were reported among the 1685 patients who received cell salvage. CONCLUSION: Use of cell salvage during cesarean delivery reduced the overall need for allogeneic blood transfusion without increasing the risk of complications, including no cases of amniotic fluid embolism.

Standard Versus Rapid Inpatient Methadone Titration for Pregnant Patients With Opioid Use Disorder: A Retrospective Cohort Study.

OBJECTIVES: Our study evaluated if rapid inpatient titration of methadone for pregnant patients with opioid use disorder (OUD) improved outcomes without increasing the risk for overdose. METHODS: This is a retrospective cohort study of pregnant patients admitted for inpatient methadone titration from January 2020 to June 2022. Outcomes were compared between standard versus rapid titration protocols. Standard titration involved an initial methadone dose with additional doses every 6 hours if clinical opiate withdrawal score (COWS) is >9. Rapid titration involved an initial methadone dose with additional doses every 4 hours if COWS is >9. The primary outcome was time required to achieve stable dose. Secondary outcomes included elopement prior to achieving stable dose, methadone-related readmission, opioid overdose, and final dose. RESULTS: There were 97 patients in the standard titration (STP) and 97 patients in the rapid titration (RTP) groups. Demographic characteristics and substance use history did not differ between the 2 groups. Time to stable dose did not differ between the 2 groups (RTP, 5.0 days ±4.0; STP, 4.0 days ±3.0; P = 0.08). Patients in the rapid titration group were less likely to elope from the hospital prior to stabilization (RTP 23.0% vs STP 37.9%, P = 0.03) and had fewer methadone-related readmissions (P < 0.001). One patient (1.0%) in the RTP group required naloxone treatment while inpatient for concern for overdose, while none did in the STP group (P = 0.32). There was no difference in median final stable dose between the 2 groups (P = 0.07). CONCLUSIONS: Rapid titration of methadone for pregnant patients with OUD was associated with decreased medical elopement and methadone-related readmission, without increasing the risk for overdose.

Glucose-6-phosphate dehydrogenase deficiency as a cause for nonimmune hydrops fetalis and severe fetal anemia: A systematic review.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder that predisposes individuals to hemolysis due to an inborn error of metabolism. We performed a systematic literature review to evaluate G6PD deficiency as a possible etiology of nonimmune hydrops fetalis (NIHF) and severe fetal anemia. METHODS: PubMed, OVID Medline, Scopus, and clinicaltrials.gov were queried from inception until 31 April 2023 for all published cases of NIHF and severe fetal anemia caused by G6PD deficiency. Keywords included "fetal edema," "hydrops fetalis," "glucose 6 phosphate dehydrogenase deficiency," and "fetal anemia." Cases with workup presuming G6PD deficiency as an etiology for NIHF and severe fetal anemia were included. PRISMA guidelines were followed. RESULTS: Five cases of G6PD-related NIHF and one case of severe fetal anemia were identified. Four fetuses (4/6, 66.7%) were male and two fetuses (2/6, 33.3%) were female. Mean gestational age at diagnosis of NIHF/anemia and delivery was 32.2 ± 4.9 and 35.7 ± 2.4 weeks, respectively. Four cases (66.7%) required a cordocentesis for fetal transfusion, and two cases (33.3%) received blood transfusions immediately following delivery. Among the four multigravida cases, two (50%) noted previous pregnancies complicated by neonatal anemia. When reported, the maternal cases included two G6PD deficiency carrier patients and two G6PD-deficient patients. Exposures to substances known to cause G6PD deficiency-related hemolysis occurred in 3/6 (50%) cases. CONCLUSION: Six cases of NIHF/severe fetal anemia were associated with G6PD deficiency. While G6PD deficiency is an X-linked recessive condition, female fetuses can be affected. Fetal G6PD deficiency testing can be considered if parental history indicates, particularly if the standard workup for NIHF is negative.

A decision analysis to determine a testing threshold for computed tomographic angiography and D-dimer in the evaluation of aortic dissection.

OBJECTIVE: The objective of this study is to determine at what probability of thoracic aortic dissection (TAD) to use a computed tomographic angiography (CTA) or a d-dimer test. METHODS: We used decision analysis software to determine the testing threshold (TT) for 3 hypothetical decisions when evaluating for TAD: (1) no testing vs CTA, (2) no testing vs D-dimer, and (3) CTA vs D-dimer. One- and 2-way sensitivity analyses were performed to determine which variables were drivers of the TTs. RESULTS: We found TTs of 0.03%, 0.013%, and 0.6% for decisions 1, 2, and 3, respectively. For all 3 decisions, patient age and the annual rate of cancer were major drivers of the TT. In decisions 1 and 2, the probability of acute renal failure requiring renal replacement therapy was a major driver, whereas d-dimer sensitivity was a major driver for decision 3. CONCLUSION: The TTs for TAD are low and reflect the large mortality benefit from diagnosis and treatment when compared with the small risks of CTA. However, given the low prevalence of TAD (~0.05% among emergency department patients presenting with symptoms previously attributed to TAD), our results suggest that without high-risk features, clinicians should not order a CTA test for TAD. Depending on age, CTA should be considered for those patients with a disease probability greater than 0.3% to 2.1%, whereas d-dimer testing is appropriate in the range of pretest probabilities from 0.01% to 0.6%. Future studies should focus on clinical decision rules that place disease probabilities below, between, and above the calculated TTs.

UNILATERAL CHEMOSIS, BULLOUS SEROUS RETINAL DETACHMENT, AND PRESUMED BACILLARY LAYER DETACHMENT IN SEVERE PREECLAMPSIA.

BACKGROUND/PURPOSE: To report a case of unilateral chemosis, serous retinal detachment (SRD), and presumed bacillary layer detachment in pregnancy. METHODS: Clinical examination and multimodal imaging findings were reviewed and analyzed. RESULTS: A 17-year-old female patient with severe preeclampsia was found to have unilateral chemosis and bullous SRD. Postpartum optical coherence tomography revealed thickened choroid and presumed bacillary layer detachment. Two weeks later, chemosis and SRD resolved, leaving behind mottled hyperpigmentation, drusen, and subretinal drusenoid deposits. CONCLUSION: The combination of chemosis and SRD in preeclampsia is exceedingly, rare and it has never previously been reported to occur unilaterally. With delivery, visual acuity, chemosis, choroidal thickness, and SRD all normalize.

Impact of Survivorship Care on Young Adult Survivors of Childhood Cancer With Post-Traumatic Stress Symptoms.

OBJECTIVES: To assess post-traumatic stress symptoms (PTSSs) in young adult survivors of childhood cancer not receiving survivorship care and to determine whether attending a survivorship-focused healthcare visit was associated with changes in PTSSs. SAMPLE & SETTING: 44 young adult survivors from the Yale Cancer Center in Connecticut without prior survivorship clinic attendance. METHODS & VARIABLES: As part of a larger trial, participants were randomized to a model of survivorship-focused health care. The University of California at Los Angeles Post-Traumatic Stress Disorder (PTSD) Reaction Index assessed PTSS severity and frequency before and after the visit. RESULTS: At baseline, almost half of the participants were classified as partial PTSD likely or PTSD likely. Many met criteria for elevated levels of individual symptoms, particularly avoidance or numbing. At follow-up, PTSSs did not differ significantly from baseline. IMPLICATIONS FOR NURSING: Survivorship care should be encouraged by nurses in healthcare settings that do not specialize in caring for long-term survivors. Nurses should facilitate screening for PTSSs and promote interventions among survivors completing cancer therapy to help them transition to survivorship care.

Health Behaviors in Cervical Cancer Survivors and Associations with Quality of Life.

PURPOSE: Improvement in health behaviors following cancer diagnosis may contribute to better prognosis and well-being. This study examines the prevalence of health behaviors in cervical cancer survivors who have completed treatment, and associations between health behaviors and quality of life (QOL). METHODS: We recruited 204 women who had completed treatment for cervical cancer to participate in a randomized counseling intervention. Participants provided information on health behaviors (smoking, physical activity, and alcohol consumption); QOL (Functional Assessment of Cancer Therapy-Cervical questionnaire); and depression (Patient-Reported Outcomes Measurement Information System), anxiety (Patient-Reported Outcomes Measurement Information System), and distress (Brief Symptom Inventory) at baseline (9-30 months after diagnosis) and subsequent to the intervention. Data were analyzed using multivariate general linear models. FINDINGS: Participants ranged in age from 20 to 72 years at diagnosis (mean = 43 years), 41% were Hispanic, and 52% were non-Hispanic white. Three-fourths were stage 1 at diagnosis and 51% were treated with radiation with or without chemotherapy. At baseline, 15% of patients were current smokers, 4% reported alcohol consumption of >10 drinks per week, and 63% reported exercising <3 hours per week. Overall, 67.4% of cervical cancer survivors did not meet recommended national guidelines for at least 1 of these health behaviors. QOL scores were significantly higher for patients with greater physical activity (128 vs 118; P = 0.002) and increased with the number of recommended guidelines met (P for trend = 0.030). Associations between patient-reported outcomes and smoking and alcohol consumption did not reach statistical significance. Participants who met guidelines for all health behaviors also had less depression (P = 0.008), anxiety (P = 0.051), and distress (P = 0.142). Participants who improved their aggregate health behaviors during the 4-month follow-up experienced a greater improvement in QOL than those who did not improve their health behaviors (10.8 vs 4.5; P = 0.026). IMPLICATIONS: Results indicate that two-thirds of cervical cancer survivors are not meeting national guidelines for smoking, physical activity, and alcohol consumption following completion of definitive treatment. These adverse health behaviors were associated with impaired QOL and higher levels of depression and distress. Positive changes in health behaviors are associated with significant improvement in QOL.