VBAC calculator 2.0: Recent evidence.

Following criticism for the use of race as a biological predictor of vaginal birth after cesarean (VBAC), an updated version of the Society for Maternal-Fetal Medicine (SMFM) VBAC calculator has been published. The variable "African American" or "Hispanic" (yes/no), which produced systematically lower chances of VBAC for nonwhites has been replaced with "chronic hypertension requiring treatment" (yes/no). Although there are no published external validation studies to date, developers report accuracy (area under the curve and calibration) nearly identical to the original calculator and it is published online for immediate use. This review examines the history of the calculator, measures of its validity, and recent studies measuring its performance among Hispanics, Blacks, Asians, and others with lower range scores. Underprediction of successful VBAC is evident in the original calculator, especially as predicted VBAC decreases. These studies raise a concern about the use of calculator scores in clinical management, that is, discouraging or restricting access to labor after cesarean (LAC) for parents with lower calculator scores. This raises special concern for minority populations who experience increased cesarean-related morbidity, face obstacles accessing LAC care, and who may benefit disproportionately from increased LAC uptake. Although calculator developers have discouraged using calculator scores to restrict access to LAC, such uses are documented. It is not clear what effect the removal of race will have on calculator performance, and further study is required before calculator scores are used in counseling. This includes studies that include large numbers of low scoring and minority patients.

Barriers to labor after cesarean: A survey of United States midwives.

INTRODUCTION: Despite calls for increased vaginal birth after cesarean (VBAC), <14% of candidates have VBAC. Requirements for documentation of scar type, and prohibitions on induction or augmentation of labor are not supported by evidence but may be widespread. The purpose of this study was to document midwives' perceptions of barriers to labor after cesarean (LAC) and their effects on midwives' ability to accommodate patient desires for LAC. METHODS: Midwives certified by the American Midwifery Certification Board (AMCB) were surveyed in 2019. Multiple option and open-ended text responses were analyzed using quantitative statistics and thematic content analysis. Select barriers to LAC, ability to accommodate LAC, and supportiveness of collaborators among midwives offering LAC were explored. RESULTS: Responses from 1398 midwives were analyzed. Eighty-four percent felt able to accommodate LAC "most of the time," and 39% reported one or more barriers to LAC. Barriers decreased ability to accommodate LAC by as much as 80%. Analysis of text responses revealed specific themes. CONCLUSIONS: Thirty-nine percent of midwives reported their practice was limited by one or more barriers that were inconsistent with professional guidelines. Imposition of barriers was driven primarily by collaborating physicians, and superceded supportive practices of midwives, nurses, and system administrators. Affected midwives were significantly less able to accommodate patient requests for LAC than those not affected. Midwives also reported pride in providing VBAC care, restrictions specific to midwifery scope of practice, and variation in physician support for LAC within practices affecting their ability to provide care.

Recovery of microbial community profile information hidden in chimeric sequence reads.

The next frontier in the field of microbiome studies is identification of all microbes present in the microbiome and accurate determination of their abundance such that microbiome profiles can serve as reliable assessments of health or disease status. PCR-based 16S rRNA gene sequencing and metagenome shotgun sequencing technologies are the prevailing approaches used in microbiome analyses. Each poses a number of technical challenges associated with PCR amplification, sample availability, and cost of processing and analysis. In general, results from these two approaches rarely agree completely with each other. Here, we compare these methods utilizing a set of vaginal swab and lavage specimens from a cohort of 42 pregnant women collected for a pilot study exploring the effect of the vaginal microbiome on preterm birth. We generated the microbial community profiles from the sequencing reads of the V3V4 and V4V5 regions of the 16S rRNA gene in the vaginal swab and lavage samples. For a subset of the vaginal samples from 12 subjects, we also performed metagenomic shotgun sequencing analysis and compared the results obtained from the PCR-based sequencing methods. Our findings suggest that sample composition and complexity, particularly at the species level, are major factors that must be considered when analyzing and interpreting microbiome data. Our approach to sequence analysis includes consideration of chimeric reads, by using our chimera-counting BlastBin program, and enables recovery of microbial content information generated during PCR-based sequencing methods, such that the microbial profiles more closely resemble those obtained from metagenomic read-based approaches.

Calculators Estimating the Likelihood of Vaginal Birth After Cesarean: Uses and Perceptions.

INTRODUCTION: A calculator estimating likelihood of vaginal birth after cesarean (VBAC) has been promoted by the Society for Maternal-Fetal Medicine, but little is known about how it is used and perceived in practice. Cutoffs for prohibiting labor after cesarean are discouraged by the calculator's developers, but such uses may be widespread. The purpose of this study was to determine how calculators predicting VBAC are used and perceived in midwifery practices. METHODS: Certified nurse-midwives and certified midwives currently providing care for labor after cesarean were surveyed between January 17, 2019, and February 7, 2019. Quantitative and text data were collected regarding the uses and perceptions of calculators among midwives and their colleagues. We compared these findings with midwives' perceptions of their ability to accommodate patient wishes for labor after cesarean. We used descriptive content analysis to evaluate themes occurring in text responses. RESULTS: There were 1305 valid responses. A requirement to use calculator scores for patient counseling was reported by 527 (40.4%) of responding midwives. Over 1 in 5 midwives reported that scores were used to discourage or prohibit labor after cesarean. Almost half reported some or strong disagreement with physician colleagues regarding calculator use. Interprofessional agreement and disagreement centered on how scores are used to direct clinical care or restrict patient options. Calculator scores were used in more than twice as many midwives' practices to discourage rather than encourage labor after cesarean. Descriptive analysis of text revealed 4 themes regarding calculators: inconsistent use, information counseling, informed consent, and influence patient management or options. DISCUSSION: Calculators predicting likelihood of VBAC success are widely used in midwifery settings and are more often used to discourage than to encourage labor after cesarean. Midwives reported both directive and nondirective counseling based on calculator scores.

Inpatient Maternal Mortality in the United States, 2002-2014.

BACKGROUND: Although prior studies of inpatient maternal mortality in the United States provide data on the overall rate and trend in inpatient maternal mortality, there are no published reports of maternal mortality data stratified by timing of its occurrence across the pregnancy continuum (antepartum, intrapartum, and postpartum). OBJECTIVE: The study objective was to determine whether the maternal mortality rate, trends over time, self-reported race/ethnicity, and associated factors vary based on the timing of the occurrence of death during pregnancy. METHODS: We conducted a cross-sectional analysis of the Nationwide Inpatient Sample database to identify pregnancy-related inpatient stays stratified by timing. Among women in the sample, we determined in-hospital mortality and used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify comorbidities and behavioral characteristics associated with mortality, including alcohol, drug, and tobacco use. Joinpoint regression was used to calculate rates and trends of in-hospital maternal mortality. RESULTS: During the study period, there were 7,411 inpatient maternal mortalities among an estimated 58,742,179 hospitalizations of women 15-49 years of age. In-hospital maternal mortality rate stratified by race showed that African Americans died at significantly higher rates during antepartum, intrapartum, and postpartum periods compared to hospitalizations for Whites or Hispanics during the same time period. Although the postpartum hospitalization represents only 2% of pregnancy-related hospitalizations among women aged 15-49 years, hospitalization during this time period accounted for 27.2% of all maternal deaths during pregnancy-related hospitalization. DISCUSSION: Most in-hospital maternal mortalities occur after hospital discharge from child birth (postpartum period). Yet, the postpartum period continues to be the time period with the least maternal healthcare surveillance in the pregnancy continuum. African American women experience three times more in-hospital mortality when compared to their White counterparts.

Meconium aspiration syndrome: Incidence and outcomes using discharge data.

BACKGROUND: Meconium aspiration syndrome (MAS) is a leading cause of morbidity and mortality among term, otherwise healthy newborns, yet population studies are rare. Definitions, outcomes and International Classification of Diseases (ICD) codes are heterogenous, complicating estimates of incidence, outcomes and risks. AIMS: To measure population incidence, risks and outcomes of MAS by ICD codes. STUDY DESIGN: Retrospective population study. SUBJECTS: Kids Inpatient Database (KID) 2012, a nationally representative weighted sample of newborn discharges in the United States. OUTCOME MEASURES: Incidence, demographic distribution, and comorbidity associated with MAS. RESULTS: In 2012 there were 9295 weighted discharges diagnosed MAS with symptoms (2.49/1000) and 4304 cases without symptoms (1.15/1000). Newborns with symptoms had nearly twice the length of stay (LOS) (6.68 vs 3.65 days, p 0.001) and nearly 3 times the total charges ($44,473 versus $15,461, p < 0.001) as those without symptoms. Incidence of death was over four times higher (7.7/1000 vs 1.7/1000, p < 0.001), persistent pulmonary hypertension 3 times higher (57.6/1000 vs 15.8/1000, p < 0.001), and hypoxic ischemic encephalopathy 5 times higher (6.2/1000 vs 1.2/1000, p < 0.001) among MAS cases with respiratory symptoms than MAS cases without respiratory symptoms. Odds ratio of MAS with symptoms was 1.54 (95% CI 1.39-1.73) for black newborns compared to whites. CONCLUSIONS: Discharge data are useful for providing population estimates of MAS incidence. Prior studies have used consolidated ICD codes for MAS (with and without respiratory symptoms), yet these represent very different disease severities. Combining MAS diagnoses with and without respiratory symptoms misrepresents incidence and disease severity, complicating comparisons of outcomes and prevention strategies.

Vulvodynia, "A Really Great Torturer": A Mixed Methods Pilot Study Examining Pain Experiences and Drug/Non-drug Pain Relief Strategies.

BACKGROUND: Women with vulvodynia, a chronic pain condition, experience vulvar pain and dyspareunia. Few studies examine the range and combination of treatment strategies that women are actually using to reduce vulvodynia. AIM: To describe pain experiences and pain relief strategies of women with vulvodynia. METHODS: Convenience sample, 60 women with vulvodynia (median age 32.5 [interquartile range {IQR} 8.5] years; 50 white, 10 racial/ethnic minorities) completed PAINReportIt and reported use of drugs and alcohol and responded to open-ended questions. Univariate descriptive statistics and bivariate inferential tests were used to describe average pain intensity scores, alcohol use, smoking, number of pain relief strategies, and their associations. Women's open-ended responses about their pain experiences and drug and non-drug pain relief strategies (NDPRS) were analyzed for patterns. OUTCOMES: Our mixed methods analysis connected data from pain measures, prescribed treatments and self-reported behaviors with women's free responses. This enabled nuanced insights into women's vulvodynia pain experiences. RESULTS: Women's descriptions of their pain and suffering aligned with their reported severe pain and attempts to control their pain, with a median pain intensity of 6.7 (IQR 2.0) despite use of adjuvant drugs (median 2.0 [IQR 2.0]), and opioids (median 1.0 [IQR 2.0]). 36 women (60%) used alcohol to lessen their pain. 26 women (43%) listed combining analgesics and alcohol to relieve their pain. 30 women (50%) smoked cigarettes. 54 women (90%) used ≥1 NDPRS. The mean number of NDPRS used was 2.1 ± 1.3 (range 0-6). The 5 most common NDPRS from women's comments were herbal medicine (40%), acupuncture (27%), massage (22%), hypnosis (15%), and mental healthcare (13%). CLINICAL IMPLICATIONS: Severe pain in women with vulvodynia may be a clinical indicator of those at higher risk of combining prescription pain medications with alcohol, which are all central nervous system depressants and may potentiate overdose. STRENGTHS AND LIMITATIONS: This pilot study demonstrated that the mixed methods approach to help understand the complexity of vulvodynia was feasible. We identified data showing a reliance on a high-risk mix of prescriptions and alcohol to reduce vulvodynia pain and a high prevalence of cigarette smoking. However, as a pilot study, these results are considered preliminary; the sample may not be representative. Perhaps only women at the extreme end of the pain continuum participated, or women took the survey twice because identifiers were not collected. CONCLUSION: Despite attempts to reduce pain using multiple therapies, including alcohol, women's vulvodynia pain is severe and not controlled. Schlaeger JM, Pauls HA, Powell-Roach KL, et al. Vulvodynia, "A Really Great Torturer": A Mixed Methods Pilot Study Examining Pain Experiences and Drug/Non-drug Pain Relief Strategies. J Sex Med 2019;16:1255-1263.

Sensory pain characteristics of vulvodynia and their association with nociceptive and neuropathic pain: an online survey pilot study.

OBJECTIVES: To evaluate self-reported sensory pain scores of women with generalized vulvodynia (GV) and provoked vestibulodynia (PVD), characterize pain phenotypes, and assess feasibility of using the Internet for recruitment and data collection among women with vulvodynia. METHODS: Descriptive online survey. Data collected using an online survey accessed via a link on the National Vulvodynia Association web site. Convenience sample, 60 women aged 18 to 45 years (mean = 32.7 ± 5.5); 50 white, 2 black/African American, 4 Hispanic/Latino, and 4 Native American/Alaskan Native, diagnosed with vulvodynia, not in menopause. Pain assessment and medication modules from PAINReportlt. RESULTS: Women with GV (n = 35) compared to PVD (n = 25). Estimated mean pain sites (2.5 ± 1.4 vs 2.2 ± 1.0, P = 0.31), mean current pain (8.7 ± 1.4 vs 5.5 ± 4.0, P = 0.0008), worst pain (8.1 ± 1.8 vs 6.1 ± 3.6, P = 0.02), and least pain in the past 24 hours (4.4 ± 1.8 vs 2.0 ± 2.0, P < 0.0001). Average pain intensity (7.1 ± 1.2 vs 4.6 ± 2.9, P = 0.0003) on a scale of 0 to 10, mean number of neuropathic words (8.3 ± 3.6 vs 7.7 ± 5.0), and mean number of nociceptive words (6.9 ± 4 vs 7.5 ± 4.4). Nineteen (54%) women with GV compared to 9 (38%) with PVD were not satisfied with pain levels. CONCLUSION: Women with GV reported severe pain, whereas those with PVD reported moderate to severe pain. Pain quality descriptors may aid a clinician's decisions about whether to prescribe adjuvant drugs vs opioids to women with vulvodynia.

CD38 expression as a prognostic indicator in chronic lymphocytic leukaemia.

Staging systems and laboratory features help predict survival in chronic lymphocytic leukaemia but they do not distinguish patients who will progress from those whose disease will remain indolent. CD38 expression has emerged as an independent prognostic factor, yet there is debate as to what level of CD38 affects prognosis. We plotted the hazard ratios for the treatment-free interval (TFI) between the higher and lower groups defined by CD38 cut-offs from 0 to 100%. The maximum hazard ratio was achieved for a cut-off of 7%. We examined by triple colour analysis the values for CD38 in 289 untreated patients using both >or=30 and >or=7% as thresholds for prognosis. Using a >or=7% threshold (but not >or=30%), we showed a significant correlation with advanced stage and male sex. The interval from diagnosis to first therapy or TFI was longer (median 36 months) in patients with <7% CD38 positive cells than those with >or= 30% (8.7 months) or with intermediate values between 7 and 29% (P<0.00005). The <7% threshold also identified patients in stage A with a long TFI (P=0.0001). Multivariate analysis showed that CD38 has independent prognostic value for TFI in all patients. In 135 patients tested for deletions of p53, 13q14 and 11q23 and for trisomy 12, we showed a correlation between 13q14 deletion and <30%/<7% CD38 positive cells and a tendency for trisomy 12 to be associated with >or=30%/>or=7% CD38 positive cells. We conclude that 7% may be a more useful threshold for disease progression than higher values of CD38.

Characterisation of TP53 abnormalities in chronic lymphocytic leukaemia.

Abnormalities of TP53 in chronic lymphocytic leukaemia (CLL) correlate with aggressive disease and transformation. We studied 115 patients with CLL including 90 untreated, 25 with heavily pretreated/refractory CLL using fluorescent in situ hybridisation (FISH) to detect allelic loss at chromosome 17p and flow cytometry (FC) to test p53 protein overexpression. A total of 17 cases were identified with TP53 deletion and/or protein expression. Both tests correlated in 10 of 17 patients; in six, one or the other abnormality was detected and in one case, with a deletion, flow cytometry failed. Material for direct DNA sequencing was available in 14 of 17 cases. Mutations were found in seven cases. Five of 14 patients with allelic loss and seven of 13 expressing p53 protein had a mutation. These were single-base substitutions and were located in exons 5, 7 or 8. Mutations were not found in 13 of 14 other cases without deletions by FISH or protein expression. The incidence of p53 abnormalities in this series was 15%, with a significant difference between untreated patients (7%) and the pretreated/refractory group (50%; P<0.01). Abnormal p53 was predicted for shorter survival, regardless of the method used. We confirm that p53 abnormalities are more common in refractory CLL and that mutations occur at the known hot spots. Testing for TP53 deletions by FISH and protein expression by FC is an effective and simple way of screening patients who are likely to have aggressive disease. DNA sequencing adds little to these methods in identifying the population at risk.

High dose methylprednisolone can induce remissions in CLL patients with p53 abnormalities.

Abnormalities of the p53 gene are known to confer detrimental effects in chronic lymphocytic leukaemia (CLL) and are associated with short survival. We have used high dose methylprednisolone (HDMP) to treat 25 patients with advanced refractory CLL of whom 45% had p53 abnormalities shown by one or more methods: flow cytometry, fluorescent in situ hybridisation and direct DNA sequencing. Fifteen were resistant to fludarabine and 16 were non-responders to their most recent therapy. Methylprednisolone had a cytotoxic effect on lymphocytes from 95% of cases assessed by an ex vivo apoptotic drug sensitivity index (DSI). HDMP was given alone or in combination with other drugs: vincristine, CCNU, Ara-C, doxorubicin, mitoxantrone and chlorambucil, according to the results of DSI. Three patients were treated twice and each treatment was analysed separately. The overall response rate was 77% with a median duration of 12 months (range 7 -23+). Responders included 5/10 with abnormal p53, of which two achieved nodular PR. Patients with p53 abnormalities fared worse than those with normal p53. There were no differences in response according to whether HDMP was used alone or in combination. Nine of the 22 evaluable patients (3 NR and 6 PR) have died from progressive disease or transformation. Main toxicity was infection in 7/25 patients. Event free and overall survival were significantly better in responders vs non-responders ( P>0.0001 and P=0.04 respectively). Patients with a DSI of 100% to steroids had a better overall and event free survival, but this was not statistically significant. This study demonstrates that HDMP alone or in combination with other agents is a useful treatment strategy in refractory CLL including patients with p53 abnormalities.