Developing a risk profile for spontaneous preterm birth and short interval to delivery among patients with threatened preterm labor

BACKGROUND: Threatened preterm birth is the most common reason for antepartum hospitalization in the United States, accounting for approximately 50% of these admissions. However, fewer than 10% of patients with inpatient evaluation for signs or symptoms of preterm labor ultimately deliver before term. OBJECTIVE: This study aimed to generate predictive models to assess the risk of preterm delivery and time to delivery based on clinical signs and symptoms of patients evaluated in our institution for preterm labor concerns. STUDY DESIGN: This was a retrospective cohort study of singleton pregnancies evaluated for signs and/or symptoms of preterm labor, including contractions, abdominal pain, vaginal bleeding, and short cervix, between 22 0/7 and 33 6/7 weeks of gestation. Inpatient evaluations were classified by patient presentation: (1) symptomatic with cervical findings (transvaginal cervical length of \u3c2.5 cm or cervical dilation of \u3e= 2.0 cm), (2) asymptomatic with cervical findings, and (3) symptomatic without cervical findings. The primary outcomes included incidence of spontaneous preterm birth and interval from presentation to delivery, compared between groups. The risk of preterm delivery was evaluated using logbinomial regression, and presentation to delivery timing was assessed by survival analysis and Cox proportional hazards modeling. RESULTS: Of 631 patients with preterm labor concerns, 96 (16%) were symptomatic with cervical findings on evaluation, 51 (8%) were asymptomatic with cervical findings, and 466 (76%) were symptomatic without cervical findings. The occurrence of preterm birth was significantly higher among symptomatic patients with cervical findings (49%) than among those with cervical findings alone (31%) or symptoms alone (11%) (P\u3c.0001). In addition, symptomatic patients with cervical findings were significantly more likely to deliver within 48 hours (20%), 1 week (30%), 2 weeks (33%), and 1 month (43%) of presentation than patients with cervical findings alone (2%, 2%, 6%, and 10%, respectively) or symptoms alone (0.4%, 1%, 1.5%, and 5%, respectively) (P value for trend\u3c.0001). Adjusted for gestational age at presentation and previous preterm birth, the overall risk of preterm delivery was significantly higher among patients with symptoms and cervical findings than among patients with cervical findings alone (relative risk, 2.81; 95% confidence interval, 1.74-4.54) or symptoms alone (relative risk, 4.39; 95% confidence interval, 3.16 -6.09). Adjusted for the same variables, symptomatic patients with cervical findings were also at higher risk of delivery over time after assessment than patients with cervical findings alone (hazard ratio, 2.06; 95% confidence interval, 1.47-2.90) or symptoms alone (hazard ratio, 2.16; 95% confidence interval, 1.74-2.70). The negative predictive value of these models suggested that only 1% of patients with isolated symptoms or cervical findings are at risk of preterm delivery within 1 week of initial presentation. CONCLUSION: Symptomatic patients with cervical findings suggestive of preterm labor were at the greatest risk of preterm birth and a shorter interval from presentation to delivery. The study findings supported a risk profile that may facilitate the selection of patients most appropriate for admission and targeted management. Nonetheless, as nearly 50% of patients meeting this risk profile subsequently deliver at term, future research is needed to identify which of these patients will require intervention

Assessing Dysferlinopathy Patients Over Three Years With a New Motor Scale

The Jain COS Consortium.[Objective] Dysferlinopathy is a muscular dystrophy with a highly variable clinical presentation and currently unpredictable progression. This variability and unpredictability presents difficulties for prognostication and clinical trial design. The Jain Clinical Outcomes Study of Dysferlinopathy aims to establish the validity of the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scale and identify factors that influence the rate of disease progression using NSAD.[Methods] We collected a longitudinal series of functional assessments from 187 patients with dysferlinopathy over 3 years. Rasch analysis was used to develop the NSAD, a motor performance scale suitable for ambulant and nonambulant patients. Generalized estimating equations were used to evaluate the impact of patient factors on outcome trajectories.[Results] The NSAD detected significant change in clinical progression over 1 year. The steepest functional decline occurred during the first 10 years after symptom onset, with more rapid decline noted in patients who developed symptoms at a younger age (p = 0.04). The most rapidly deteriorating group over the study was patients 3 to 8 years post symptom onset at baseline.[Interpretation] The NSAD is the first validated limb girdle specific scale of motor performance, suitable for use in clinical practice and clinical trials. Longitudinal analysis showed it may be possible to identify patient factors associated with greater functional decline both across the disease course and in the short-term for clinical trial preparation. Through further work and validation in this cohort, we anticipate that a disease model incorporating functional performance will allow for more accurate prognosis for patients with dysferlinopathy. ANN NEUROL 2021;89:967–978The estimated US $4 million needed to fund this study was provided by the Jain Foundation. (www.jain-foundation.org) The Jain COS consortium would like to thank the study participants and their families for their invaluable contribution. The John Walton Centre Muscular Dystrophy Research Centre is part of the MRC Centre for Neuromuscular Diseases (Grant number MR/K000608/1).Peer reviewe

Assessment of disease progression in dysferlinopathy: A 1-year cohort study

ObjectiveTo assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.MethodsOne hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis.ResultsThe functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint.ConclusionCertain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials.ClinicalTrials.gov identifier:NCT01676077

Assessing dysferlinopathy patients over three years with a new motor scale

OBJECTIVE: Dysferlinopathy is a muscular dystrophy with a highly variable clinical presentation and currently unpredictable progression. This variability and unpredictability presents difficulties for prognostication and clinical trial design. The Jain Clinical Outcomes Study of Dysferlinopathy aims to establish the validity of the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scale and identify factors that influence the rate of disease progression using NSAD. METHODS: We collected a longitudinal series of functional assessments from 187 dysferlinopathy patients over three years. Rasch analysis was used to develop the NSAD, a motor performance scale suitable for ambulant and non-ambulant patients. Generalized estimating equations were used to evaluate the impact of patient factors on outcome trajectories. RESULTS: The NSAD detected significant change in clinical progression over 1 year. The steepest functional decline occurred during the first 10 years after symptom onset, with more rapid decline noted in patients who developed symptoms at a younger age (p = 0.04). The most rapidly deteriorating group over the study was patients 3-8 years post symptom onset at baseline. INTERPRETATION: The NSAD is the first validated limb girdle specific scale of motor performance, suitable for use in clinics practice and clinical trials. Longitudinal analysis showed it may be possible to identify patient factors associated with greater functional decline both across the disease course and in the short-term for clinical trial preparation. Through further work and validation in this cohort, we anticipate that a disease model incorporating functional performance will allow for more accurate prognosis for patients with dysferlinopathy

Assessing the relationship of patient reported outcome measures with functional status in dysferlinopathy: a Rasch analysis approach

Dysferlinopathy is a muscular dystrophy with a highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims to identify the suitability of PROMs and their association with motor performance.Two-hundred and four patients with dysferlinopathy were identified in the Jain Foundation's Clinical Outcome Study in Dysferlinopathy from 14 sites in 8 countries. All patients completed the following PROMs: Individualized Neuromuscular Quality of Life Questionnaire (INQoL), International Physical Activity Questionnaire (IPAQ), and activity limitations for patients with upper and/or lower limb impairments (ACTIVLIMs). In addition, nonambulant patients completed the Egen Klassifikation Scale (EK). Assessments were conducted annually at baseline, years 1, 2, 3, and 4. Data were also collected on the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) and Performance of Upper Limb (PUL) at these time points from year 2. Data were analyzed using descriptive statistics and Rasch analysis was conducted on ACTIVLIM, EK, INQoL. For associations, graphs (NSAD with ACTIVLIM, IPAQ and INQoL and EK with PUL) were generated from generalized estimating equations (GEE). The ACTIVLIM appeared robust psychometrically and was strongly associated with the NSAD total score (Pseudo R(2) 0.68). The INQoL performed less well and was poorly associated with the NSAD total score (Pseudo R(2) 0.18). EK scores were strongly associated with PUL (Pseudo R(2) 0.69). IPAQ was poorly associated with NSAD scores (Pseudo R(2) 0.09). This study showed that several of the chosen PROMs demonstrated change over time and a good association with functional outcomes. An alternative quality of life measure and method of collecting data on physical activity may need to be selected for assessing dysferlinopathy

Equivalency of in vitro fertilization success rates in elective single blastocyst transfer and elective double blastocyst transfer: An example of equivalence methodology in clinical reproductive health

Context: When comparing success rates between treatments, it is more appropriate to structure analyses in terms of equivalence rather than traditional analyses that assess differences. Unfortunately, no studies of elective single blastocyst transfer (eSBT) have been conducted in this manner. Aims: The objective of this study was to assess clinical equivalence of in vitro fertilization success rates among patients undergoing eSBT. Settings and Design: A historical prospective study was conducted at a private fertility center. Methods: Medical records were reviewed to identify patients eligible for eSBT. Equivalency of success rates, defined as no more than a 10% difference based on 95% confidence intervals (CIs), was compared between eSBT (n = 125) and eDBT (n = 213) groups. Results: Using traditional analysis techniques, no differences in pregnancy or live-birth rates were seen (eSBT: 84.6% vs. eDBT: 84.5%, P = 0.99; eSBT: 65.3% vs. eDBT: 72.3%, P = 0.23). The 95% CI around the difference in pregnancy rates ranged from -7.9 to 8.1, suggesting clinically equivalent pregnancy rates. Clinical equivalence was not established for live-births (95% CI = −18.5–4.5). Conclusions: Findings suggest comparable pregnancy rates can be achieved in a clinical setting when utilizing eSBT in good-prognosis patients. Although live-birth rate equivalence was not demonstrated, it is thought the additional complications associated with multiple gestations outweigh the potentially higher live-birth rate. The present study highlights the importance of utilizing equivalence analyses when making statements regarding the similarity of two treatments in reproductive health, rather than relying on superiority analyses alone

Risk Factors for Complications in Children with Staphylococcus aureus Bacteremia

Objectives: To determine risk factors for complications in children with Staphylococcus aureus (S aureus) bacteremia, including methicillin resistance. Study design: Single center, retrospective cohort study of children 6418 years of age hospitalized with S aureus bacteremia. We compared clinical characteristics and outcomes between those with methicillin-sensitive S aureus (MSSA) and methicillin-resistant S aureus (MRSA) bacteremia. Multivariate regression models identified risk factors associated with developing complications and with longer duration of bacteremia. Results: We identified 394 episodes of S aureus bacteremia, 279 (70.8%) with MSSA, and 115 (29.2%) with MRSA. Primary site of infection was catheter-related in 34%, musculoskeletal in 30%, skin/soft tissue in 10.2%, pneumonia in 6.4%, and endovascular in 6.6%. Eight children (2.0%) died within 30 days because of S aureus bacteremia, 15 (3.5%) had recurrence within 30 days, and 38 (9.6%) had complications including septic emboli or a metastatic focus of infection. Methicillin resistance was associated with development of a complication (aOR 3.31; 95% CI 1.60-6.85), and catheter-related infections were less likely to be associated with a complication (aOR 0.40; 95% CI 0.15-1.03). In a Poisson regression analysis on duration of bacteremia, methicillin resistance, musculoskeletal infection, endovascular infection, black race, and delayed intervention for source control were significantly associated with longer duration of bacteremia. Conclusions: In this cohort of children with S aureus bacteremia, MRSA infections ere associated with longer duration of bacteremia and a higher likelihood of complications

Multigenerational Cardiometabolic Risk as a Predictor of Birth Outcomes: The Bogalusa Heart Study.

OBJECTIVE: To examine the relationship between generation 1 (grandmaternal) cardiometabolic risk factors and generation 3 (grandchild’s) birthweight and gestational age STUDY DESIGN: Mother-daughter pairs in the Bogalusa Heart Study (1973-present) were linked to their children’s birth certificates; women were also interviewed about their reproductive histories, creating a three-generation linkage including 177 generation 1 (grandmothers), 210 generation 2 (mothers), and 424 generation 3 children. Pre-pregnancy cardiometabolic risk factors (BMI, lipids, glucose) for generation 1 (mean age 16.2) and 2 (mean age 11.1) were examined as predictors of generation 3 birthweight and gestational age using linear and logistic regression with adjustment for age, race, parity, and other confounders. RESULTS: Generation 2 higher BMI was associated with higher birthweight (28 g per 1 unit, 95% CI 12–44) and gestational age (0.08 weeks, 95% CI 0.02–0.14) in generation 3, and generation 1 higher BMI was associated with higher birthweight (52 g, 95% CI 34–70)) in the generation 2. Generation 1’s higher glucose levels were associated with higher birthweight in generation 3 (adjusted beta 111 g, 95% CI 33–189), and triglycerides (adjusted beta −21, 95% CI −43-0) and LDL (adjusted beta −24, 95% CI −48-0) were associated with lower birthweight. CONCLUSIONS: These results suggest the possibility of multigenerational developmental programming of birth outcomes, although mechanisms (whether biological or environmental) are undetermined