Hemolytic disease of the fetus and newborn in the sensitizing pregnancy where anti-D was incorrectly identified as RhIG.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a potentially fatal complication in Rh-incompatible pregnancies and rarely occurs in the sensitizing pregnancy. Distinguishing RhIG from true anti-D identified is challenging. A case of severe HDFN in which a sample drawn at 28 weeks showed anti-D antibody (3+ strength) attributed to RhIG is described. RBC antibody testing early in pregnancy was negative. At birth, the infant was severely anemic and maternal anti-D titer was 1:256. This case represents a clinically significant anti-D in the sensitizing pregnancy that was missed due to confusion with RhIG. METHODS: To determine if agglutination strength could be helpful, a retrospective chart-review using both electronic and paper medical records was performed on 348 samples identified as RhIG and 52 true anti-D samples. The agglutination strength of antibody was recorded for each sample. RESULTS: For RhIG, there was an even distribution between the weak to moderate agglutination strength (w+, 1+, and 2+) results (35%, 26%, and 33%, respectively) and just 6% had a 3+ strength. Agglutination strength in patients with high titer (≥1:16) anti-D showed they often (44.4%) have 1+ or 2+ agglutination reactivity. CONCLUSIONS: These results show that agglutination strength alone does not provide reliable evidence to distinguish RhIG from high titer anti-D antibodies. We recommend that in cases where there is any uncertainty about whether the anti-D reactivity is due to RhIG, titers should be performed to rule out clinically significant anti-D antibody.

Rigor, reproducibility, and transparency of randomized controlled trials in obstetrics and gynecology.

BACKGROUND: Randomized controlled trials are considered the highest level of evidence but fewer than half are reproducible. A rigorous methodology improves trial quality, but reproducibility may be limited by a lack of transparency in reporting. The Consolidated Standards of Reporting Trials guidelines define reporting standards, and pretrial registration requires a predefined methodology and predefined outcomes. OBJECTIVE: We evaluated obstetrics and gynecology trials published in 6 journals in terms of their adherence to the Consolidated Standards of Reporting Trials guidelines. Second, we evaluated pretrial registration compliance and concordance between the registry and publication. Furthermore, we evaluated the differences in trial characteristics among randomized controlled trials with the highest level of compliance and those with lower levels of compliance and adherence to guidelines by journal type. STUDY DESIGN: This was a cross-sectional study of obstetrics and gynecology trials published between 2017 and 2019 in 6 journals (American Journal of Obstetrics & Gynecology, BJOG: An International Journal of Obstetrics and Gynaecology, Obstetrics & Gynecology, The Journal of the American Medical Association, The Lancet, and The New England Journal of Medicine). Randomized controlled trials were identified via PubMed and manual journal archive searches. The primary outcome was adequate compliance with the Consolidated Standards of Reporting Trials guidelines defined as ≥80% of the checklist items present. Secondary outcomes included completion of pretrial registration and concordance between the pretrial registration and publication in terms of the outcomes and sample size. We compared the characteristics between trials with adequate compliance and those with inadequate compliance. Secondary analyses included comparisons of characteristics of the trials in the top quartile for compliance with the Consolidated Standards of Reporting Trials guidelines with those of the trials in lower quartiles and compliance with guidelines in obstetrics-gynecology vs non-obstetrics-gynecology journals. In an exploratory analysis, trends in compliance with the Consolidated Standards of Reporting Trials guidelines across the study period were assessed. A post hoc sensitivity analysis evaluated the outcomes after the exclusion of 2 retracted trials. RESULTS: Of the 170 trials included, 80% (95% confidence interval, 74%-86%) were adequately compliant with the Consolidated Standards of Reporting Trials manuscript guidelines and 66% (95% confidence interval, 59%-73%) were compliant with the abstract guidelines. Nearly all trials (98%) reported pretrial registration. Concordance between pretrial registration and publication in terms of the primary outcomes was identified for 77% of the trials, concordance in terms of the secondary outcomes was observed in 32% of the trials, and concordance in terms of sample size was observed in 60% of the trials. Trials with adequate compliance were more likely to be preregistered, include an a priori power calculation, and use an intent to treat analysis. Trials in the top quartile for compliance with the Consolidated Standards of Reporting Trials guidelines were more likely to be multicenter, international, and government funded. More trials from non-obstetrics-gynecology journals were in the top quartile for compliance with the Consolidated Standards of Reporting Trials guidelines than trials from obstetrics-gynecology journals (64.9% vs 25.7%; P<.001). No significant trends in adequate compliance were identified across the study period. Results did not differ significantly in the sensitivity analysis. CONCLUSION: Of all the trials included, 20% of obstetrics-gynecology trials published in 6 high-impact journals were not compliant with the Consolidated Standards of Reporting Trials guidelines, and there were major discrepancies between pretrial registration and publication. Transparency, reproducibility, and scientific rigor in obstetrics and gynecology trial reporting needs to be improved.

Impact of the p-Value Threshold on Interpretation of Trial Outcomes in Obstetrics and Gynecology.

OBJECTIVE: Randomized controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. However, the reproducibility crisis has raised concerns about the scientific rigor of published RCT findings. Some advocate for a lower p-value threshold. We aimed to review published OB/Gyn topical RCTs in three representative OB/Gyn journals and three high impact non-OB/Gyn journals to determine if their interpretations would change with adoption of a p-value threshold for significance of 0.005. Secondarily, we evaluated if there were differences in methodologic characteristics between those that did and did not lose significance. STUDY DESIGN: A manual search was performed to identify all OB/Gyn RCTs published in the selected journals between July 2017 and June 2019. Data were collected on primary outcome(s), methodology, and p-values. We determined the proportion of primary outcomes that would remain statistically significant with adoption of a p-value significance threshold of 0.005 versus be reinterpreted as "suggestive" (defined as p-value between 0.005 and 0.05). Chi-square or Fisher's exact test were used to compare study characteristics. RESULTS: Overall, 202 RCTs met inclusion criteria; 52% in obstetrics and 48% in gynecology. Of 90 studies considered significant with p <0.05 at the time of publication, 54.4% (n = 49) would maintain significant (p < 0.005), while 45.6% (n = 41) would become suggestive using the lower threshold. Most RCTs utilized a single (90.1%) versus composite (8.9%) primary outcome type, used an intent-to-treat analysis (73.3%), and studied a drug intervention (46.5%). Methodologically, 23.7% did not prespecify analysis type, 28.2% did not meet the pre-determined sample size, and 9.4% did not report an a priori sample size calculation. Studies maintaining significance were more likely to be international and report a funding source. CONCLUSION: Adopting a p-value significance threshold of 0.005 would require reinterpretation of almost half of RCT results in the OB/Gyn literature. Highly variable methodological quality was identified. KEY POINTS: · New p-value threshold results in reinterpretation of nearly half of RCT results in OB/Gyn literature.. · Highly variable methodological quality was identified.. · Reduced use of binary interpretations of significance is necessary..

Increased risk of neonatal complications and infections in children of kidney-transplanted women: A nationwide controlled cohort study.

Information related to short- and long-term risks of children born to kidney-transplanted women remains limited. With the aim of investigating the risk of neonatal complications, and the short- and long-term risk of infections in offspring of kidney-transplanted women, all children born to kidney-transplanted women in Denmark from 1964 to 2016 were identified in a nationwide retrospective matched cohort study. A total of 124 children of kidney-transplanted women were identified and matched on gender, birth year, and number of siblings at birth 1:10 with children born to nontransplanted women identified in the Danish general population. Prevalence of low birth weight (37.9%, risk ratio [RR] = 12.61; 95% confidence interval [CI], 8.5-18.5), premature birth (46.0%, RR = 11.32; 95% CI, 8.1-15.7) and malformations (11.3%, RR = 1.98; 95% CI, 1.2-3.4) was increased in children of kidney-transplanted women compared with controls. Similarly, prevalence of hospitalization due to infection was increased during the first year of life (21.0%, RR = 1.94; 95% CI, 1.3-2.8), from age 1 to 5 (34.2%, RR = 1.89; 95% CI, 1.4-2.5), and overall (41.9%, RR = 1.67; 95% CI, 1.3-2.1). The risk of infection was also higher in children of kidney-transplanted mothers born preterm or with low birth weight compared with similar controls. In conclusion, risk of neonatal complications, malformations, and both early and late infection were increased in children born to kidney-transplanted women.

Contributions, Aspirations, and Challenges of Academic Specialist Divisions in Obstetrics and Gynecology.

Shortly after its inception, the Society for Academic Specialists in General Obstetrics and Gynecology recognized that no data described the composition and faculty activities of "academic generalist divisions." Consequently, in 2018, the Society for Academic Specialists in General Obstetrics and Gynecology appointed a presidential task force and conducted the current surveys of chairs and division directors and key informant interviews to understand the composition and faculty activities in divisions of academic specialists in departments of obstetrics and gynecology and propose criteria for excellence in each mission area to guide development of divisions. In 2014, with Society for Academic Specialists in General Obstetrics and Gynecology's guidance, these divisions were referred to as academic specialists divisions and the faculty within as academic specialists to emphasize that they provide specialized women's health care in academic settings. The divisions comprised approximately 30% of departments' full-time faculty (median 12). In 27% of the departments, these divisions contributed more than half of departmental revenue, and 49% contributed 26-50%. Nearly 90% of divisions provided a sizeable proportion of the department's total teaching efforts. Compensation relied more on clinical productivity than on seniority, quality, academic contributions, or academic rank. Subsequently, five performance domains were identified to help divisions define divisional excellence: clinical, education, research, service & advocacy, and academic environment. Furthermore, excellent divisions were characterized as those with outstanding clinicians and educators who emphasize scholarly productivity. Although academic specialists contribute significantly to their departments' financial, clinical, and educational productivity, many have limited opportunities for scholarly activity. Achieving divisional excellence likely will depend on the ability to recruit and retain faculty with career expectations that align with the division's prioritized performance domains.

Patient factors influence surgical options in gastroparesis.

BACKGROUND: Patient selection for the diverse surgical procedures for gastroparesis remains poorly defined. Our aim was to evaluate how patient factors have determined our surgical approach to gastroparesis. METHODS: 95 patients undergoing 105 surgical procedures for gastroparesis were reviewed. Patient factors were compared across six surgical procedures: gastric neurostimulator, pyloroplasty, neurostimulator plus pyloroplasty, sleeve gastrectomy, gastric bypass and gastrectomy. Global symptom severity was determined preoperatively and at last follow up. RESULTS: There were significant differences in etiology, BMI and gastroesophageal reflux across the various operations. Patients undergoing pyloroplasty and gastrectomy; were more likely to have a postsurgical etiology. (p < .05) Patients undergoing sleeve gastrectomy and gastric bypass were more likely to have BMI >35. (p <.05) Those undergoing sleeve gastrectomy were less likely to have gastroesophageal reflux preoperatively. (p <.05) There was no difference in preoperative clinical stage across the procedures. CONCLUSION: Patient factors influence choice of procedure in the surgical treatment of gastroparesis. Etiology of gastroparesis, BMI >35 and gastroesophageal reflux are important determinants.

Reproductive immunology from the perspective of the clinician.

Investigators generate new and innovative ideas needed to advance knowledge, while physicians want proven treatments that provide the best care for their patients. Along with advances in reproductive immunology research, there have also been controversies such as immunologic treatments for recurrent pregnancy loss. Research deficiencies that are wasteful and misleading include: over-interpretation and extrapolation from animal studies to the human, inadequate sample sizes, lack of appropriate control groups, use of surrogate markers, associations presented as causation, un-blinded testing and treatments, unreproducible results, and non-standardized outcomes. The purpose of the EQUATOR Network (Enhancing the QUAlity Of health Research) is to improve the quality of research and its publication. These guidelines (CONSORT, STROBE, PRISMA, STARD, ARRIVE) have been accepted as mandatory by virtually all major medical journals, and all investigators should prospectively incorporate them into their study designs. From the perspective of a clinician-scientist and an editor, my premise is that the purpose of much basic science research and all clinical research is to improve the medical care of patients. Unproven and costly diagnostic tests and treatments for potential immunologic clinical problems can no longer be justified. The primary and most important outcome that should be reported for all pregnancy-related immunologic studies is the live birth rate of a healthy infant. Today's clinicians and patients expect unbiased research that leads to evidence-based recommendations for practical and effective treatments.

Validating Evidence and Using Standard Outcomes for Recurrent Pregnancy Loss Tests and Treatments.

Unproven diagnostic tests and treatments for recurrent pregnancy loss patients can no longer be justified. The use of accepted study guidelines for conducting randomized trials, observational studies, systematic reviews and meta-analyses, diagnostic tests, animal research, and the development of standardized consensus derived outcomes would greatly improve the quality of recurrent pregnancy loss studies and their reporting.

Multi-service highly sensitive rectifier for enhanced RF energy scavenging.

Due to the growing implications of energy costs and carbon footprints, the need to adopt inexpensive, green energy harvesting strategies are of paramount importance for the long-term conservation of the environment and the global economy. To address this, the feasibility of harvesting low power density ambient RF energy simultaneously from multiple sources is examined. A high efficiency multi-resonant rectifier is proposed, which operates at two frequency bands (478-496 and 852-869 MHz) and exhibits favorable impedance matching over a broad input power range (-40 to -10 dBm). Simulation and experimental results of input reflection coefficient and rectified output power are in excellent agreement, demonstrating the usefulness of this innovative low-power rectification technique. Measurement results indicate an effective efficiency of 54.3%, and an output DC voltage of 772.8 mV is achieved for a multi-tone input power of -10 dBm. Furthermore, the measured output DC power from harvesting RF energy from multiple services concurrently exhibits a 3.14 and 7.24 fold increase over single frequency rectification at 490 and 860 MHz respectively. Therefore, the proposed multi-service highly sensitive rectifier is a promising technique for providing a sustainable energy source for low power applications in urban environments.

Immunotherapy for recurrent miscarriage.

BACKGROUND: Because immunological aberrations might be the cause of miscarriage in some women, several immunotherapies have been used to treat women with otherwise unexplained recurrent pregnancy loss. OBJECTIVES: The objective of this review was to assess the effects of any immunotherapy, including paternal leukocyte immunization and intravenous immunoglobulin on the live birth rate in women with previous unexplained recurrent miscarriages. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (11 February 2014) and reference lists of retrieved studies. SELECTION CRITERIA: Randomized trials of immunotherapies used to treat women with three or more prior miscarriages and no more than one live birth after, in whom all recognized non-immunologic causes of recurrent miscarriage had been ruled out and no simultaneous treatment was given. DATA COLLECTION AND ANALYSIS: The review author and the two co-authors independently extracted data and assessed study quality for all studies considered for this review. MAIN RESULTS: Twenty trials of high quality were included. The various forms of immunotherapy did not show significant differences between treatment and control groups in terms of subsequent live births: paternal cell immunization (12 trials, 641 women), Peto odds ratio (Peto OR) 1.23, 95% confidence interval (CI) 0.89 to 1.70; third-party donor cell immunization (three trials, 156 women), Peto OR 1.39, 95% CI 0.68 to 2.82; trophoblast membrane infusion (one trial, 37 women), Peto OR 0.40, 95% CI 0.11 to 1.45; or intravenous immunoglobulin, (eight trials, 303 women), Peto OR 0.98, 95% CI 0.61 to 1.58. AUTHORS' CONCLUSIONS: Paternal cell immunization, third-party donor leukocytes, trophoblast membranes, and intravenous immunoglobulin provide no significant beneficial effect over placebo in improving the live birth rate.

The numbers game: evaluation of statistics by obstetrics & gynecology.

Statistical analysis has become integral to the planning, conduct, and reporting of modern medical research. Attention to the statistical aspects of manuscripts submitted to Obstetrics & Gynecology goes back approximately 40 years and the process used in their evaluation has evolved over that time. For the past 20 years, submissions with any type of statistics and being seriously considered for acceptance have routinely been reviewed by a Statistical Editor who judges the work on a number of statistical and design characteristics. Findings of the statistical design review (which has been done by one Statistical Editor over the entire 20-year period) are integrated into the editorial decision about acceptance. The statistical review generally leads to rejection of approximately 16-25% of manuscripts and in a larger proportion, it identifies less serious problems, the correction of which improves the final product.

NIH consensus development conference: diagnosing gestational diabetes mellitus.

OBJECTIVE: To provide healthcare providers, patients, and the general public with a responsible assessment of currently available data on diagnosing gestational diabetes mellitus (GDM). PARTICIPANTS: A non-U.S. Department of Health and Human Services, nonadvocate 15-member panel representing the fields of obstetrics and gynecology, maternal-fetal medicine, pediatrics, diabetic research, biostatistics, women's health issues, health services research, decision analysis, health management and policy, health economics, epidemiology, and community engagement. In addition, 16 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the University of Alberta Evidence-based Practice Centre, through the Agency for Healthcare Research and Quality (AHRQ). Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was posted at http://prevention.nih.gov/ for public comment and the panel released a final statement approximately 10 weeks later. The final statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: At present, GDM is commonly diagnosed in the United States using a 1-hour screening test with a 50-gram glucose load followed by a 3-hour 100-gram glucose tolerance test (a two-step approach) for those found to be abnormal on the screen. This approach identifies approximately 5% to 6% of the population as having GDM. In contrast, newly proposed diagnostic strategies rely on the administration of a 2-hour glucose tolerance test (a one-step approach) with a fasting component and a 75-gram glucose load. These strategies differ on whether a 1-hour sample is included, whether two abnormal values are required, and the diagnostic cutoffs that are used. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) has proposed diagnostic thresholds based on demonstrated associations between glycemic levels and an increased risk of obstetric and perinatal morbidities. The panel considered whether a one-step approach to the diagnosis of GDM should be adopted in place of the two-step approach. The one-step approach offers certain operational advantages. The current two-step approach is used only during pregnancy and is largely restricted to the United States. There would be value in a consistent, international diagnostic standard across one's lifespan. This unification would allow better standardization of best practices in patient care and comparability of research outcomes. The one-step approach also holds potential advantages for women and their health care providers, as it would allow a diagnosis to be achieved within the context of one visit as opposed to two. However, the one-step approach, as proposed by the IADPSG, is anticipated to increase the frequency of the diagnosis of GDM by twofold to threefold, to a prevalence of approximately 15% to 20%. There are several concerns regarding the diagnosis of GDM in these additional women. It is not well understood whether the additional women identified by this approach will benefit from treatment, and if so, to what extent. Moreover, the care of these women will generate additional direct and indirect health care costs. There is also evidence that the labeling of these women may have unintended consequences, such as an increase in cesarean delivery and more intensive newborn assessments. In addition, increased patient costs, life disruptions, and psychosocial burdens have been identified. Available studies do not provide clear evidence that a one-step approach is cost-effective in comparison with the current two-step approach. After much deliberation, the panel believes that there are clear benefits to international standardization with regard to the one-step approach. Nevertheless, at present, the panel believes that there is not sufficient evidence to adopt a one-step approach. The panel is particularly concerned about the adoption of new criteria that would increase the prevalence of GDM, and the corresponding costs and interventions, without clear demonstration of improvements in the most clinically important health and patient-centered outcomes. Thus, the panel recommends that the two-step approach be continued. However, given the potential benefits of a one-step approach, resolution of the uncertainties associated with its use would warrant revision of this conclusion.