Postpartum Family Planning in Pediatrics: A Survey of Parental Contraceptive Needs and Health Services Preferences.

OBJECTIVE: Infant well-child visits are increasingly being explored as opportunities to address parental postpartum health needs, including those related to reproductive health. To inform potential pediatric clinic-based interventions, this study assessed postpartum contraceptive needs and health services preferences. METHODS: We surveyed postpartum individuals attending 2 to 6-month well-child visits at three Northern California pediatric clinics (2019-20). We examined unmet contraceptive needs; the acceptability of contraceptive education, counseling, and provision at well-child visits; and sociodemographic and clinical correlates. We conducted univariate and multivariable regression modeling to assess associations between sociodemographic and clinical variables, the status of contraceptive needs, and acceptability measures. RESULTS: Study participants (n = 263) were diverse in terms of race and ethnicity (13% Asian, 9% Black, 37% Latinx, 12% Multi-racial or Other, 29% White), and socioeconomic status. Overall, 25% had unmet contraceptive needs. Unmet need was more common among participants who had delivered more recently, were multiparous, or reported ≥ 1 barrier to obtaining contraception; postpartum visit attendance, education, race, and ethnicity were not associated with unmet need. Most participants deemed the following acceptable in the pediatric clinic: receiving contraceptive information (85%), discussing contraception (86%), and obtaining a contraceptive method (81%). Acceptability of these services was greater among participants with unmet contraceptive needs, better self-rated health, and private insurance (all P < .05). CONCLUSIONS: A quarter of participants had unmet contraceptive needs beyond the early postpartum period. Most considered the pediatric clinic an acceptable place to address contraception, suggesting the pediatric clinic may be a suitable setting for interventions aiming to prevent undesired pregnancies and their sequelae.

Fetal sex differences in human chorionic gonadotropin fluctuate by maternal race, age, weight and by gestational age.

Circulating levels of the placental glycoprotein hormone human chorionic gonadotropin (hCG) are higher in women carrying female v. male fetuses; yet, the significance of this difference with respect to maternal factors, environmental exposures and neonatal outcomes is unknown. As a first step in evaluating the biologic and clinical significance of sex differences in hCG, we conducted a population-level analysis to assess its stability across subgroups. Subjects were women carrying singleton pregnancies who participated in prenatal and newborn screening programs in CA from 2009 to 2012 (1.1 million serum samples). hCG was measured in the first and second trimesters and fetal sex was determined from the neonatal record. Multivariate linear models were used to estimate hCG means in women carrying female and male fetuses. We report fluctuations in the ratios of female to male hCG by maternal factors and by gestational age. hCG was higher in the case of a female fetus by 11 and 8% in the first and second trimesters, respectively (P<0.0001). There were small (1-5%) fluctuations in the sex difference by maternal race, weight and age. The female-to-male ratio in hCG decreased from 17 to 2% in the first trimester, and then increased from 2 to 19% in the second trimester (P<0.0001). We demonstrate within a well enumerated, diverse US population that the sex difference in hCG overall is stable. Small fluctuations within population subgroups may be relevant to environmental and physiologic effects on the placenta and can be probed further using these types of data.

A cautionary tale: dealing with missing data in clinical trials for rheumatic diseases.

OBJECTIVES: Missing data are found in nearly all clinical trials and it is important to use appropriate statistical techniques to analyse clinical trials with missing data. We discuss common statistical methods for tackling missing data and how to handle results when the analyses give different results. METHODS: Using data from a placebo-controlled, randomised bovine Type I collagen (CI) study in diffuse cutaneous systemic sclerosis (dcSSc), we apply different statistical approaches to handling missing data. We also describe simple ways to ascertain the type of missing data in the data set, to the extent possible. RESULTS: We examine eleven different methods to impute missing data. An analysis based on completers alone (complete case analysis and available case analysis) and the last observation carried forward (LOCF) methods require underlying assumptions which are rarely met in practice. Multiple imputation, mixed effects, and repeated measures try to account for the differences among patients and account for patient's specific response patterns, although the assumption that the missing data is directly related to the observed characteristics may well not be true. The joint likelihood based model combines the mixed effect model and logistic regression model to explicitly handle data not missing at random and so it is more realistic and potentially takes an additional step toward decreasing bias. CONCLUSIONS: We discussed various ways of handling missing data and provide recommendations on how to arrive at a conclusion when different statistical approaches to analyse missing data analysis in clinical trials give conflicting answers.

Patterns of chronic co-morbid medical conditions in older residents of U.S. nursing homes: differences between the sexes and across the agespan.

OBJECTIVE: There are limited data on combinations of co-morbid conditions to guide efforts to improve therapeutic strategies in patients with multiple co-morbid conditions. To some extent, this may be due to limited data on combinations of co-morbid conditions in patient groups. Our goal was to determine the most common co-morbid medical conditions in older residents of U.S. nursing homes and identify sex differences in prevalences and changes across the agespan of nursing residents. DESIGN: Cross sectional analysis of National Nursing Home Survey (NNHS)--a nationally representative sample with comprehensive medical data on nursing home residents. SETTING: 1174 Nursing homes. PARTICIPANTS: Long term stay residents of U.S. Nursing Homes aged 65 years and older (11,734 :8745 women, 2989 men). MEASUREMENTS: Determination of the prevalences of the most frequent two and three disease combinations identified using Clinical Classifications Software (CCS) for ICD-9-CM and a composite vascular disease diagnosis (atherosclerosis and/or coronary artery disease, and/or peripheral arterial disease, and/or cerebrovascular disease or stroke) from the most recent and only NNHS survey with comprehensive medical diagnosis information. RESULTS: Frequent 2-disease combinations were: hypertension (HTN) + dementia (DEM) in 27%, HTN + any Vascular (Vasc) disease (26%), HTN + depression(DEP) 21%, HTN + arthritis(ARTH) 20%, DEM + Vasc (21%), DEM+Depression 19%, Arthritis + DEM 17%, DEP + Vasc (16%), ARTH + Vasc (15%), followed by HTN + GERD (14%) and ARTH + DEP (14%). Frequent 3-disease combinations: HTN +VASC+ DEP in 13%, HTN +DEM +DEP (11%), and HTN+Arthritis+DEM (10%). HTN was in 80% of the top 3-disease combinations, Vasc in 50%, HTN+VASC in 35%, DEM or DEP in 40%, ARTH in 25% and GERD in 20%. Combinations with anemia, arthritis, dementia, heart failure, osteroporosis, thyroid disease were higher in women, COPD combinations higher in men. As age increased, dementia, depression, arthritis, and anemia with hypertension were common co-morbid combinations, diabetes and heart failure were not. CONCLUSIONS: Hypertension, vascular disease, dementia, arthritis, depression, and gastro-esophageal reflux disease were part of the most prevalent co-morbid conditions. Multimorbidity patterns can be identified in nursing home residents and vary with age and by sex.

Factors affecting sunscreen use and sun avoidance in a U.S. national sample of organ transplant recipients.

BACKGROUND: Organ transplant recipients have an increased risk of nonmelanoma skin cancers due to immunosuppressive therapy following transplantation. Use of sunscreen has been shown to reduce this risk. OBJECTIVES: To identify patient and healthcare factors associated with sun-protective behaviours in organ transplant recipients after transplantation with the goal of increasing overall sunscreen use. METHODS: This study utilized a cross-sectional, retrospective survey from a national sample of 198 organ transplant recipients in the U.S.A. from 2004 to 2008 with no prior diagnosis of skin cancer. The main outcome measures were sunscreen use and sun avoidance before and after transplantation. Frequency of sunscreen use and sun exposure was obtained by self-report on Likert scales ranging from never to always, and these responses were converted to a numerical scale from 0 to 4. RESULTS: Overall sunscreen use increased after transplantation (from a score of 1·4 to 2·1, P < 0·001). Sex, Fitzpatrick skin type, receiving advice to avoid sun from a healthcare provider, and pretransplantation sunscreen use were significantly associated with frequency of post-transplantation sunscreen use in multivariate models. Pretransplantation sun exposure, advice to avoid sun and pretransplantation sunscreen use were significantly associated with sun avoidance post-transplantation. CONCLUSIONS: Both patient features and clinician advice are associated with sun-protective behaviours after organ transplantation. These results will help physicians target expanded sun-protection counselling to those patients most in need of such intervention.

Examining the effect of hospital-level factors on mortality of very low birth weight infants using multilevel modeling.

OBJECTIVE: The objective of this study was to examine the effect of hospital-level factors on mortality of very low birth weight infants using multilevel modeling. STUDY DESIGN: This is a secondary data analysis of California maternal-infant hospital discharge data from 1997 to 2002. The study population was limited to singleton, non-anomalous, very low birth weight infants, who delivered in hospitals providing neonatal intensive care services (level-2 and higher). Hierarchical generalized linear modeling, also known as multilevel modeling, was used to adjust for individual-level confounders. RESULT: In a multilevel model, increasing hospital volume of very low birth weight deliveries was associated with lower odds of very low birth weight mortality. Characteristics of a particular hospital's obstetrical and neonatal services (the presence of residency and fellowship training programs and the availability of perinatal and neonatal services) had no independent effect. CONCLUSION: Using multilevel modeling, hospital volume of very low birth weight deliveries appears to be the primary driver of reduced mortality among very low birth weight infants.

Handling missing data issues in clinical trials for rheumatic diseases.

Missing data are ubiquitous in clinical trials for rheumatic diseases, and it is important to accommodate them using appropriate statistical techniques. We review some of the basic considerations for missing data and survey a range of statistical techniques for analysis of longitudinal clinical trial data with missingness. Using clinical trial data from patients with diffuse systemic sclerosis, we show that different approaches to handling missing data can lead to different conclusions on the efficacy of the treatment. We then suggest how such discrepancies might be addressed. In particular, we emphasize that the commonly used method in rheumatic clinical trials of carrying the last observation forward to impute missing values should not be the primary analysis. We review software for analyzing different types of missing data and discuss our freely available software library for analyzing the more difficult but more realistic situation when the probability of dropout or missing data may depend on the unobserved missing value.

Relationship between valve opening pressure, body position, and intracranial pressure in normal pressure hydrocephalus: paradigm for selection of programmable valve pressure setting.

OBJECTIVE: There is little scientific basis for guidance in selecting the optimal valve for the treatment of normal pressure hydrocephalus. The aim of this study was to determine the programmable valve opening pressure setting that would result in a slight reduction in intracranial pressure (ICP) after a ventriculoperitoneal shunt is implanted. We also assessed whether shunt-induced ICP could be predicted on the basis of a simple hydrodynamic equation. METHODS: In this prospective study of 11 patients with normal pressure hydrocephalus, ICP was measured before and after implantation of a shunt incorporating a programmable valve without an antisiphon device. Pressure measurements, including intraperitoneal pressure, were recorded at body angles ranging from 0 to 55 degrees and at valve settings ranging from 30 to 200 mm H(2)O. Measured ICP values were compared with values computed using a simple hydrodynamic equation. RESULTS: Even at a valve setting greater than the mean baseline ICP (200 mm H(2)O), the supine ICP was significantly lower than the baseline value (baseline ICP, 164 +/- 64 mm H(2)O; postoperative ICP, 125 +/- 69 mm H(2)O, P = 0.04). Valve pressure did not equate 1:1 with the measured postoperative ICP. Comprehensive ICP measurements at upright body positions demonstrated a stepwise reduction in ICP rather than a precipitous decline as a result of so-called siphoning. CONCLUSION: This study indicates that very high valve opening pressure settings may be optimal for the initial treatment of normal pressure hydrocephalus. The relationship between ICP and opening pressure valves is linear but not predicted by simple hydrodynamics.

Decreased recovery of CD4 lymphocytes in older HIV-infected patients beginning highly active antiretroviral therapy.

Among virological responders, the area under the curve of the CD4 count minus baseline (AUCMB) after 3, 9, 15 and 18 months of highly active antiretroviral therapy (HAART) was less in individuals 55 years or older (P < 0.05). Fewer older individuals achieved increases of 50, 100, or over 150 CD4 cells/l. A random quadratic time course model estimated that the AUCMB decreased 35 cells/year for each 10 years of additional age during the first 12 months after HAART (P < 0.005).

Carbon dioxide reactivity, pressure autoregulation, and metabolic suppression reactivity after head injury: a transcranial Doppler study.

OBJECT: Contemporary management of head-injured patients is based on assumptions about CO2 reactivity, pressure autoregulation (PA), and vascular reactivity to pharmacological metabolic suppression. In this study, serial assessments of vasoreactivity of the middle cerebral artery (MCA) were performed using bilateral transcranial Doppler (TCD) ultrasonography. METHODS: Twenty-eight patients (mean age 33 +/- 13 years, median Glasgow Coma Scale score of 7) underwent a total of 61 testing sessions during postinjury Days 0 to 13. The CO2 reactivity (58 studies in 28 patients), PA (51 studies in 23 patients), and metabolic suppression reactivity (35 studies in 16 patients) were quantified for each cerebral hemisphere by measuring changes in MCA velocity in response to transient hyperventilation, arterial blood pressure elevation, or propofol-induced burst suppression, respectively. One or both hemispheres registered below normal vasoreactivity scores in 40%, 69%, and 97% of study sessions for CO2 reactivity, PA, and metabolic suppression reactivity (p < 0.0001), respectively. Intracranial hypertension, classified as intracranial pressure (ICP) greater than 20 mm Hg at the time of testing, was associated with global impairment of CO2 reactivity, PA, and metabolic suppression reactivity (p < 0.05). A low baseline cerebral perfusion pressure (CPP) was also predictive of impaired CO2 reactivity and PA (p < 0.01). Early postinjury hypotension or hypoxia was also associated with impaired CO2 reactivity (p < 0.05), and hemorrhagic brain lesions in or overlying the MCA territory were predictive of impaired metabolic suppression reactivity (p < 0.01). The 6-month Glasgow Outcome Scale score correlated with the overall degree of impaired vasoreactivity (p < 0.05). CONCLUSIONS: During the first 2 weeks after moderate or severe head injury, CO2 reactivity remains relatively intact, PA is variably impaired, and metabolic suppression reactivity remains severely impaired. Elevated ICP appears to affect all three components of vasoreactivity that were tested, whereas other clinical factors such as CPP, hypotensive and hypoxic insults, and hemorrhagic brain lesions have distinctly different impacts on the state of vasoreactivity. Incorporation of TCD ultrasonography-derived vasoreactivity data may facilitate more injury- and time-specific therapies for head-injured patients.

Effect of cytokines on HIV-induced depletion of thymocytes in vivo.

BACKGROUND: Cytokines play an important role in the differentiation of thymocytes into mature T cells; consequently, certain cytokines could be useful for immune reconstitution after HIV infection without increasing viral load. OBJECTIVE: To investigate whether cytokines affect immune depletion caused by HIV infection with a CXCR4-tropic strain in SCID-hu mice implanted with human fetal thymus and liver (thy/liv) tissue. METHODS: The thy/liv implants were either mock infected or infected with HIV-1 NL4-3, a CXCR4-tropic molecular clone. Interleukin (IL)-2, IL-4, IL-7, interferon-gamma (IFN-gamma) or diluent was administered to the mice during the second and third week postinfection. Viral load and immunophenotype were determined in thymocytes. RESULTS: Thymocyte subset distributions at 3 weeks postinfection were significantly influenced by treatment with certain cytokines. In particular, IL-2 caused the infected mice to retain a thymocyte profile that was more similar to that in mock-infected mice than that in diluent-treated infected mice, in that the percentages of immature CD4+CD8+ and CD5+CD1+ cells were slightly higher and much less variable than in diluent-treated infected mice. The effect of IFN-gamma treatment was similar to IL-2 but did not reach statistical significance. However, after IFN-gamma treatment, normal percentages of mature CD3+CD69+ cells were maintained whereas this population was relatively increased in diluent-treated infected mice. Although treatment with IL-4 and IL-7 delayed depletion of immature thymocytes, these cytokines increased viral load. CONCLUSIONS: Cytokines such as IL-2 and IFN-gamma maintain immature thymocytes without increasing viral load and may be useful as adjuncts to improve immune reconstitution after HIV infection.

Longitudinal models for AIDS marker data.

Over the past decade, researchers have put a great amount of effort into developing suitable models for the analysis of longitudinal CD4 data and other markers of AIDS progression. These models must be general enough to allow for different patterns of change in the marker data. In this paper, we review the existing literature including our preferred models which involve mixed effects, stochastic terms and independent measurement error. Adding stochastic terms to standard mixed effects models gives an interpretable and parsimonious method for generalizing the covariance structure of the measurement error and short-term variability. We focus on univariate and bivariate models with integrated Ornstein-Uhlenbeck (IOU) stochastic terms. The IOU process allows for a range of biologically plausible derivative tracking that encompasses both random trajectory and Brownian motion behaviour. We illustrate these modelling techniques on longitudinal CD4 and viral RNA data.