Effect of Body Mass Index on Complications After Vaginal and Laparoscopic Apical Prolapse Surgery.

INTRODUCTION AND HYPOTHESIS: Obesity is increasing worldwide, and data are limited on how body mass index (BMI) affects surgical risk in pelvic organ prolapse. This study is aimed at evaluating the impact of obesity on outcomes after apical pelvic organ prolapse surgery. We hypothesize that obese patients have higher rates of postoperative complications. METHODS: This is a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2014 to 2018. Current Procedural Terminology codes identified subjects aged 18-89 who underwent apical prolapse repair, including vaginal colpopexy and laparoscopic or robotic sacrocolpopexy. Minor and major complications were analyzed using the World Health Organization BMI category. Regression analysis was performed to adjust for confounders. RESULTS: The total cohort was 24,718 with 15,137 vaginal colpopexy and 9,581 laparoscopic/robotic sacrocolpopexy. The average age was 60.1, 76.5% were white, 24.2% were American Society of Anesthesiologists (ASA) class 3 or 4, and 44.7% had a major medical comorbidity. Eight hundred and eighty-five patients (5.4%) experienced a minor complication, 324 (2.0%) a major complication, and 1,167 (7.2%) any complication. There was no difference in any, major, or minor complication by BMI and this persisted after adjusting for age, race, ASA class, smoking, and surgical approach. CONCLUSIONS: There is no difference in complication rates after apical prolapse surgery by BMI regardless of age, race, ASA class, smoking use, and surgical approach. Patients and surgeons should be reassured that minimally invasive apical prolapse surgery is safe, with low complication rates. Randomized controlled trials are needed to verify these findings.

Brain cholesterol metabolism and Parkinson's disease.

BACKGROUND: Circulating cholesterol levels have been linked to PD, but not directly to brain physiology. OBJECTIVE: To assess whether brain cholesterol metabolism is related to PD. METHODS: Sixty PD patients and 64 controls were recruited from an academic movement disorder clinic (2009-2012). Thirty-five PD patients and 33 controls returned approximately 36 months later. Fasting plasma (S)24-OH-cholesterol (brain-derived cholesterol metabolite) and 27-OH-cholesterol (peripheral cholesterol metabolite) were quantified. Odds ratios for PD were derived from logistic regression models, adjusting for potential confounders. Relationships between the oxysterols and clinical measurements were explored using Spearman correlation coefficients. RESULTS: Mean age of PD subjects was 63.8 ± 8.3 years and disease duration was 5.0 ± 5.4 years. Plasma (S)24-OH-cholesterol levels were inversely associated with the odds of having PD, with an odds ratio of 0.92 (95% confidence interval: 0.87-0.97) for each 1-ng/mL increase (P = 0.004). Compared to the lowest tertile, the odds ratio was 0.34 (0.12-0.98) for the second tertile (P = 0.045) and 0.08 (0.02-0.31) for the highest tertile (P < 0.001). Higher (S)24-OH-cholesterol levels also were correlated with better sense of smell (r = 0.35; P = 0.01). No significant associations were found between clinical measures and 27-OH-cholesterol, a peripheral cholesterol metabolite. Furthermore, (S)24-OH-cholesterol levels were stable over time, whereas 27-OH-cholesterol decreased with time in both cases and controls. CONCLUSIONS: Results indicate that plasma (S)24-OH-cholesterol (possibly reflecting brain cholesterol metabolism) is inversely linked to PD, is relatively stable over time, and may serve as a new biomarker for PD. Further investigation is necessary to determine the mechanistic and clinical implications. © 2019 International Parkinson and Movement Disorder Society.

Exclusion of Reproductive-aged Women in COVID-19 Vaccination and Clinical Trials.

INTRODUCTION: We analyzed the exclusion of pregnant and breastfeeding individuals and those capable of pregnancy in COVID-19 vaccine and clinical treatment trials. METHODS: Inclusion and exclusion criteria were extracted from all listed COVID-19 vaccine and treatment clinical trials from May 1, 2020, to October 31, 2020, using the U.S. National Library of Medicine database. We report rates of rates of exclusion for pregnant and lactating individuals and requirements for contraception for pregnancy-capable participants in COVID-19 vaccine and treatment clinical trials. The analysis included the association between clinical trial exclusion and vaccine and treatment type, study location, sponsor, and phase. RESULTS: Pregnant and lactating individuals were explicitly excluded from most COVID-19 vaccine and treatment clinical trials. Of the 90 vaccine trials, 88 (97.8%) excluded pregnant individuals, 73 (81.1%) excluded lactating individuals, and 56 (62.2%) required contraception use. Of the 495 treatment trials, 350 (70.7%) excluded pregnant individuals, 269 (54.3%) excluded lactating individuals, and 91 (18.4%) required contraception use. Although vaccine type was not associated with pregnancy exclusion, it was associated with lactation exclusion (p = .01) and contraception requirement (p < .001). Treatment type was associated with pregnancy exclusion, lactation exclusion, and contraception requirement (all p < .001). CONCLUSIONS: COVID-19 vaccination and treatment clinical trials mirrored historical trends restricting participation owing to pregnancy, lactation, and contraception nonuse, despite known safety profiles. People of childbearing potential should be considered for and afforded the same opportunity as males to make informed decisions on study participation, particularly in the setting of a global pandemic.

Impact of tracheostomy timing on outcome after severe head injury.

BACKGROUND: The influence of tracheostomy timing on outcome after severe head injury remains controversial. METHODS: The investigation was based on data prospectively collected by the Pennsylvania Trauma Society Foundation statewide trauma registry from January 1990 until December 2005. RESULTS: 3,104 patients met criteria for inclusion in the study (GCS ≤ 8 and tracheostomy). Early Tracheostomy Group (ETG) patients, defined as tracheostomy performed during hospital days 1-7, were more likely to be functionally independent at discharge (adjusted odds ratio (OR) 1.45, 95% confidence interval (CI), 1.16-1.82, P = 0.001) and have a shorter length of stay (adjusted OR 0.23, 95% CI, 0.20-0.28, P < 0.0001). However, Late Tracheostomy Group (LTG) patients, defined as tracheostomy performed >7 days after admission, were approximately twice as likely to be discharged alive (adjusted OR 2.12, 95% CI, 1.60-2.82, P < 0.0001). Using a Composite Outcome Scale, which combined these three measures, there was a non-significant trend toward a higher likelihood of a poor outcome in LTG patients. When this analysis was repeated using only those patients in relatively good condition on admission, LTG patients were found to be approximately 50% less likely to have a good outcome (adjusted OR 0.46, 95% CI, 0.28-0.73, P = 0.001) when compared to ETG patients. CONCLUSIONS: These results indicate a complex relationship between tracheostomy timing and outcome, but suggest that a strategy of early tracheostomy, particularly when performed on patients with a reasonable chance of survival, results in a better overall clinical outcome than when the tracheostomy is performed in a delayed manner.

Surgical simulation supplements reproductive endocrinology and infertility fellowship training.

OBJECTIVE: To assess if a surgical boot camp improves laparoscopic skill among reproduction endocrinology and infertility (REI) fellows and increases fellow desire to incorporate surgical skills into practice and to examine whether fellowship in vitro fertilization (IVF) volume correlates with surgical efficiency. DESIGN: Prospective evaluation. SETTING: Simulation Center. PATIENTS: Forty REI fellows. INTERVENTIONS: Fellows were timed before and after training in laparoscopic suturing and knot tying and while using virtual simulators. Fellows were surveyed before boot camp on prior experience with IVF and reproductive surgery, and immediately and 1 month after boot camp on their desire to incorporate surgical skills into practice. MAIN OUTCOME MEASURES: Efficiency of laparoscopic suturing and knot tying before and after boot camp; likelihood and persistence of incorporating surgical skills into practice immediately and 1 month after boot camp; and correlation between fellowship IVF volume and fellow surgical efficiency. RESULTS: Fellows experienced significant improvement in laparoscopic suturing (44 sec), intracorporeal knot tying (82 sec), and extracorporeal knot tying (71 sec). Fellows reported being more likely to incorporate operative hysteroscopy (89%), operative laparoscopy (87%), and laparoscopic suturing (84%) into practice immediately following boot camp with no difference 1 month later. Fifty-four percent of fellows reported being more likely to perform robotic surgery after the boot camp, increasing to 70% 1 month later. There were weak correlations between IVF case volume and efficiency in laparoscopic suturing or hysteroscopic polypectomy (Spearman correlation coefficients, -0.14 and -0.03). CONCLUSIONS: An intensive surgical boot camp enhances surgical skill among REI fellows.

Pregnancy registry: three-year follow-up of children conceived from letrozole, clomiphene, or gonadotropins.

OBJECTIVE: To study the development of children conceived from non-IVF infertility treatments consisting of gonadotropins, clomiphene, or letrozole. DESIGN: Prospective cohort study. SETTING: U.S. academic health centers. PATIENT(S): Children of women with polycystic ovary syndrome who conceived with letrozole (LTZ) or clomiphene (CC) in the PPCOS II study or women with unexplained infertility (AMIGOS study) who conceived with LTZ, CC, or gonadotropin (GN). INTERVENTION(S): Longitudinal annual follow-up from birth to age 3. MAIN OUTCOME MEASURE(S): Scores from Ages and Stages Developmental Questionnaire (ASQ), MacArthur-Bates Communicative Development Inventory (MCDI), and annual growth. RESULT(S): One hundred eighty-five children from 160 families participated in at least one follow-up evaluation from the two infertility trials. Most multiple gestations in the follow-up study resulted from GN treatment (n = 14) followed by CC (n = 6) and LTZ (n = 3). There were no significant differences among the three groups at any time point with respect to abnormal scores on the ASQ. On the MCDI Words and Gestures, the LTZ group scored significantly higher than the GN group for most items (phrases, early gestures, later gestures, and total gestures). Children in the CC group scored significantly higher than the GN group for the later gestures and total gestures items. CONCLUSION(S): Differences in growth and cognitive developmental rates among children conceived with first-line infertility therapies, including LTZ, are relatively minor and likely due to differences in multiple pregnancy rates.

Urine markers do not predict biopsy findings or presence of bladder ulcers in interstitial cystitis/painful bladder syndrome.

PURPOSE: We tested for associations between urine markers, bladder biopsy features and bladder ulcers in interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: Subjects were 72 patients with interstitial cystitis/painful bladder syndrome undergoing bladder distention and biopsy. Urine was collected before the procedure. Urine marker levels were correlated with biopsy and cystoscopic findings. Patients with no previous interstitial cystitis/painful bladder syndrome treatments (47) were analyzed separately from previously treated patients (25). RESULTS: For untreated patients urine interleukin-6 and cyclic guanosine monophosphate were associated with urothelial epidermal growth factor receptor staining (for interleukin-6 r = 0.29; 95% CI 0.07, 0.51; p = 0.01 and for cyclic guanosine monophosphate r = 0.34; 95% CI 0.13, 0.55; p = 0.002). Urine interleukin-8 was negatively associated with urothelial heparin-binding epidermal growth factor-like growth factor staining (r = -0.34; 95% CI -0.55, -0.12; p = 0.002) and positively associated with lamina propria mast cell count (r = 0.29; 95% CI 0.06, 0.52; p = 0.01). The latter association also was seen in treated patients (r = 0.46; 95% CI 0.20, 0.73; p <0.001). None of the urine markers was significantly different for ulcer vs nonulcer groups. All of the patients with ulcer had extensive inflammation on bladder biopsy including severe mononuclear cell infiltration, moderate or strong interleukin-6 staining in the urothelium and lamina propria, and leukocyte common antigen staining in more than 10% of the lamina propria. However, these features also were seen in 24% to 76% of the patients without ulcer. CONCLUSIONS: Overall urine markers did not associate robustly with biopsy findings. The strongest association was a positive association between urine interleukin-8 levels and bladder mast cell count. Patients with ulcer consistently had bladder inflammation but the cystoscopic finding of ulcers was not a sensitive indicator of inflammation on bladder biopsy.

Association of a Postnatal Parent Education Program for Abusive Head Trauma With Subsequent Pediatric Abusive Head Trauma Hospitalization Rates.

Importance: Studies suggest that a postnatal parental intervention may reduce the incidence of abusive head trauma (AHT) of infants and young children. Objective: To assess the effect of statewide universal AHT education for parents on AHT hospitalization rates in Pennsylvania and on parents' self-reported knowledge gains and parenting behaviors. Design, Setting, and Participants: Changes in AHT hospitalization rates in Pennsylvania before and during the intervention were compared with those in 5 other states lacking universal parental AHT education during the same period. Data were collected from maternity units and birthing centers throughout Pennsylvania from the parents of 1 593 834 infants born on these units from January 1, 2003, to December 31, 2013. Parental behavior and knowledge were assessed through immediate (n = 16 111) and 7-month postintervention (n = 146) parent surveys in a per protocol analysis of evaluable parents. Interventions: Parents read a brochure, viewed an 8-minute video about infant crying and AHT, asked questions of the nurse, and signed a commitment statement affirming their participation. Educational posters were displayed on each unit. Main Outcomes and Measures: Changes in AHT hospitalization rates before and during the intervention in Pennsylvania and 5 other states. Secondary outcomes included self-reported knowledge gains and changes in parenting practices. Results: A total of 1 180 291 parents (74.1%) of children ranging in age from 0 to 23 months signed a commitment statement. Incidence rate ratios for hospitalization for AHT increased in Pennsylvania from 24.1 (95% CI, 22.1-26.3) to 26.6 (95% CI, 24.9-28.4) per 100 000 children aged 0 to 23 months during the intervention period; changes in Pennsylvania were not significantly different from aggregate changes in the 5 other states, from 22.4 (95% CI, 21.2-23.6) to 22.0 (95% CI, 21.2-22.8) per 100 000 children aged 0 to 23 months. A total of 16 111 parents (21.5% men, 78.5% women) completed the postnatal survey. Despite an overall 74.1% adherence with the intervention, only 20.6% of parents saw the brochure and video and only 5.7% were exposed to the entire intervention. Among the respondents answering individual questions on the postnatal surveys, 10 958 mothers (91.0%) and 2950 fathers (88.6%) reported learning a lot about understanding infant crying as normal; 11 023 mothers (92.2%) and 2923 fathers (88.9%), calming their infant, 11 396 mothers (94.6%) and 3035 fathers (91.9%), calming themselves; 10 060 mothers (85.1%) and 2688 fathers (83.4%), selecting other infant caregivers; and 11 435 mothers (94.8%) and 3201 fathers (95.8%), that the information would decrease the likelihood of shaking an infant. Among the 143 respondents completing the 7-month survey, 109 (76.2%) reported remembering the information while their child was crying. Conclusions and Relevance: This intervention was not associated with a reduction in pediatric AHT hospitalization rates but was associated with self-reported gains in parental knowledge that were retained for 7 months.

Incomplete and inconsistent reporting of maternal and fetal outcomes in infertility treatment trials.

Pregnancy outcomes and adverse outcomes in infertility trials are reported to varying extents; for example, 35% of clinical trials reported no information on pregnancy loss, only 43% reported adverse events during the preconception treatment period, and only 7% reported any serious adverse events. Incomplete reporting limits the value of these studies in counseling patients on the risk-benefit ratio of treatment to themselves and their infants.

Associations of birthweight and gestational age with reproductive and metabolic phenotypes in women with polycystic ovarian syndrome and their first-degree relatives.

CONTEXT: Low birthweight has been associated with metabolic and reproductive abnormalities in adults. OBJECTIVE: The aim of the study was to examine the relationship between birthweight and gestational age and its association with reproductive and metabolic phenotypes in women with PCOS and their first-degree relatives. DESIGN AND SETTING: We conducted a family-based study of PCOS at an academic health center. PATIENTS OR OTHER PARTICIPANTS: A total of 1038 individuals (845 females and 193 males) from the cohort and 168 controls participated in the study. MAIN OUTCOME MEASURES: The association between birthweight and familial phenotype was measured. RESULTS: Self-reported and actual birthweight were highly correlated [Spearman correlation coefficient (r) = 0.81; 95% CI, 0.66, 0.89; P = 0.001) and concordant (concordance correlation coefficient = 0.86; 95% lower limit = 0.78). We noted that birthweight for both genders in PCOS families and controls fell within the 10th and 90th percentiles for gestational age based on U.S. population norms. The 50th percentiles for a gestational age of 40 wk were very similar (3409 g in PCOS, 3455 g for controls, and 3495 g for the United States). There were no significant associations between phenotype and birthweight in PCOS probands. Furthermore, there were not any significant relationships between phenotype and birthweight in female or male family members of the PCOS probands. CONCLUSIONS: Birthweight in PCOS families mirrors control and U.S. population data, even corrected for gestational age, and has no substantive association with reproductive and metabolic abnormalities in women with PCOS, their female relatives, or their male relatives.