First-Trimester Crown-Rump Length and Embryonic Volume of Fetuses with Structural Congenital Abnormalities Measured in Virtual Reality: An Observational Study.

Background. With the introduction of three-dimensional (3D) ultrasound it has become possible to measure volumes. The relative increase in embryonic volume (EV) is much larger than that of the crown-rump length (CRL) over the same time period. We examined whether EV is a better parameter to determine growth restriction in fetuses with structural congenital abnormalities. Study Design, Subjects, and Outcome Measures. CRL and EV were measured using a Virtual Reality (VR) system in prospectively collected 3D ultrasound volumes of 56 fetuses diagnosed with structural congenital abnormalities in the first trimester of pregnancy (gestational age 7+5 to 14+5 weeks). Measured CRL and EV were converted to z-scores and to percentages of the expected mean using previously published reference curves of euploid fetuses. The one-sample t-test was performed to test significance. Results. The EV was smaller than expected for GA in fetuses with structural congenital abnormalities (-35% p < 0.001, z-score -1.44 p < 0.001), whereas CRL was not (-6.43% p = 0.118, z-score -0.43 p = 0.605). Conclusions. CRL is a less reliable parameter to determine growth restriction in fetuses with structural congenital abnormalities as compared with EV. By measuring EV, growth restriction in first-trimester fetuses with structural congenital abnormalities becomes more evident and enables an earlier detection of these cases.

Growth trajectories of the human embryonic head and periconceptional maternal conditions.

STUDY QUESTION: Can growth trajectories of the human embryonic head be created using 3D ultrasound (3D-US) and virtual reality (VR) technology, and be associated with second trimester fetal head size and periconceptional maternal conditions? SUMMARY ANSWER: Serial first trimester head circumference (HC) and head volume (HV) measurements were used to create reliable growth trajectories of the embryonic head, which were significantly associated with fetal head size and periconceptional maternal smoking, age and ITALIC! in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) treatment. WHAT IS KNOWN ALREADY: Fetal growth is influenced by periconceptional maternal conditions. STUDY DESIGN, SIZE, DURATION: We selected 149 singleton pregnancies with a live born non-malformed fetus from the Rotterdam periconception cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Bi-parietal diameter and occipital frontal diameter to calculate HC, HV and crown-rump length (CRL) were measured weekly between 9 + 0 and 12 + 6 weeks gestational age (GA) using 3D-US and VR. Fetal HC was obtained from second trimester structural anomaly scans. Growth trajectories of the embryonic head were created with general additive models and linear mixed models were used to estimate associations with maternal periconceptional conditions as a function of GA and CRL, respectively. MAIN RESULTS: A total of 303 3D-US images of 149 pregnancies were eligible for embryonic head measurements (intra-class correlation coefficients >0.99). Associations were found between embryonic HC and fetal HC ( ITALIC! ρ = 0.617, ITALIC! P < 0.001) and between embryonic HV and fetal HC ( ITALIC! ρ = 0.660, ITALIC! P < 0.001) in ITALIC! Z-scores. Maternal periconceptional smoking was associated with decreased, and maternal age and IVF/ICSI treatment with increased growth trajectories of the embryonic head measured by HC and HV (All ITALIC! P < 0.05). LIMITATIONS, REASONS FOR CAUTION: The consequences of the small effect sizes for neurodevelopmental outcome need further investigation. As the study population consists largely of tertiary hospital patients, external validity should be studied in the general population. WIDER IMPLICATIONS OF THE FINDINGS: Assessment of growth trajectories of the embryonic head may be of benefit in future early antenatal care. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre and Sophia Foundation for Medical Research, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared.

First-trimester crown-rump length and embryonic volume of aneuploid fetuses measured in virtual reality.

OBJECTIVES: To examine whether embryonic volume (EV), as measured using three-dimensional (3D) ultrasound and a virtual reality approach, is a better measure of growth restriction than is crown-rump length (CRL) in aneuploid fetuses. METHODS: We retrospectively measured CRL and EV in prospectively collected 3D ultrasound volumes of 55 aneuploid fetuses using the Barco I-Space VR system. The gestational age ranged from 11 + 2 to 14 + 4 weeks. We compared our measured data with previously published reference curves for euploid fetuses. Delta-values were calculated by subtracting the expected mean for euploid fetuses of the same gestational age from observed values. The one-sample t-test was used to test the significance of differences observed. RESULTS: The CRL measurements of fetuses with trisomy 21 (n = 26), trisomy 13 (n = 5) and monosomy X (n = 5) were comparable with those of euploid fetuses, but in fetuses with trisomy 18 (n = 19) the CRL was 14.5% smaller (P < 0.001). The EV in fetuses with trisomies 21, 18 and 13 and monosomy X was smaller than in euploid fetuses (-27.8%, P < 0.001; -39.4%, P < 0.001; -40.9%, P = 0.004; and -27.3%, P = 0.055, respectively). CONCLUSIONS: When relying on CRL measurements alone, first-trimester growth restriction is especially manifest in trisomy 18. Using EV, growth restriction is also evident in trisomies 21 and 13 and monosomy X. EV seems to be a more effective measurement for the assessment of first-trimester growth restriction in aneuploid fetuses.

Indinavir concentrations and antiviral effect.

STUDY OBJECTIVES: To determine the variability of indinavir pharmacokinetics in patients attending an outpatient clinic, and to explore relationships between indinavir exposure and antiviral effect. DESIGN: Open, formal pharmacokinetic evaluation. SETTING: University-affiliated clinical research center. PATIENTS: Forty-three adults infected with the human immunodeficiency virus (HIV) receiving therapy with indinavir and concomitant nucleoside reverse transcriptase inhibitors. INTERVENTION: Indinavir concentrations were measured after patients were observed taking an 800-mg oral dose, and pharmacokinetic parameters were determined using a one-compartment oral absorption model. Virologic and pharmacologic characteristics were compared in a subset of 23 patients who were protease inhibitor naive before receiving indinavir. MEASUREMENTS AND MAIN RESULTS: Mean indinavir pharmacokinetics were similar to those reported previously. Significant intersubject variability in systemic exposure was observed in patients receiving the same dosage; the 8-hour area under the curve (AUC8) ranged from 5.4-68.0 microM x hour. In protease inhibitor-naive subjects, the indinavir AUC8 was statistically higher in those with undetectable plasma HIV RNA (30.7 microM x hr) versus detectable plasma HIV RNA (22.4 microM x hr, p=0.035). Measured concentrations 5 hours after the dose and extrapolated 8-hour concentrations were also significantly higher in patients with undetectable plasma HIV RNA (both p=0.007). CONCLUSIONS: Indinavir plasma concentrations were highly variable among patients receiving the same dosage. Patients with an undetectable plasma HIV RNA level who were protease inhibitor naive had statistically higher indinavir concentrations and slower oral clearance than the group with detectable HIV RNA. Relationships between indinavir concentrations and anti-HIV effect provide a basis for quantifying the pharmacologic contribution to the heterogeneity in therapeutic response.

Validation of self-report of influenza and pneumococcal vaccination status in elderly outpatients.

OBJECTIVE: To assess the validity of self-reported influenza and pneumococcal vaccination status. DESIGN: Cross-sectional surveys of outpatients aged 65 years or older. SETTING: A Veterans Affairs Medical Center (VA) and a community managed care organization (MCO). Both organizations have organized influenza and pneumococcal vaccination programs. SUBJECTS: VA subjects included all elderly respondents to a mailed survey of 500 randomly selected outpatients. MCO subjects included all respondents to a telephone survey of 300 randomly selected elderly members of the MCO. MEASUREMENTS: The VA survey was conducted following the 1995-1996 influenza season while the MCO survey was conducted following the 1994-1995 season. Self-report from the mailed survey for VA subjects and from the telephone survey for MCO subjects was compared to medical record documentation (paper and computerized combined). RESULTS: The response rate was 77% (n = 369) for the VA subjects of whom 195 (53%) were aged 65 or older. The response rate for the MCO subjects was 84% (n = 237). Self-report of influenza vaccination had a sensitivity (SENS) of 1.0 and a specificity (SPEC) of .79 with a kappa of .72 (95% CI .58-.86) among VA patients. Among MCO patients, self-report of influenza vaccination had a SENS of .98 and a SPEC of .71 with kappa of .75 (95% CI .69-.89). Self-report of pneumococcal vaccination status among VA patients had a SENS of .97 and a SPEC of .53 with a kappa of .42 (95% CI .32-.52). Among MCO patients, self-report of pneumococcal vaccination had a SENS of .90 and a SPEC of .64 with a kappa of .54 (95% CI .40-.68). A secondary analysis excluding subjects living outside of the VA's catchment area improved the specificity and indices of concordance of self-report of both influenza and pneumococcal vaccination. A secondary analysis of MCO data which excluded subjects who received a pneumococcal vaccination > 2 years prior to the study also improved concordance and the negative predictive value of self-report. CONCLUSIONS: Self-report of influenza vaccination is a highly sensitive and moderately specific measure. Self-report of pneumococcal vaccination is also a highly sensitive but less specific measure of vaccination status. Lower rates of validity for pneumococcal vaccination may reflect both less accurate recall, particularly for more distant vaccination, and less complete documentation in medical records.

Relation between influenza vaccination and outpatient visits, hospitalization, and mortality in elderly persons with chronic lung disease.

BACKGROUND: Influenza vaccine is underused in groups targeted for vaccination. OBJECTIVE: To define the effects of influenza and the benefits of influenza vaccination in elderly persons with chronic lung disease. DESIGN: Retrospective, multiseason cohort study. SETTING: Large managed care organization. PATIENTS: All elderly members of a managed care organization who had a previous diagnosis of chronic lung disease. MEASUREMENTS: Outcomes in vaccinated and unvaccinated persons for the 1993-1994, 1994-1995, and 1995-1996 influenza seasons were compared after adjustment for baseline demographic and health characteristics. All data were obtained from administrative databases. RESULTS: Vaccination rates were greater than 70% for each season. Among unvaccinated persons, hospitalization rates for pneumonia and influenza were twice as high in the influenza seasons as they were in the interim (noninfluenza) periods. Influenza vaccination was associated with fewer hospitalizations for pneumonia and influenza (adjusted risk ratio, 0.48 [95% CI, 0.28 to 0.82]) and with lower risk for death (adjusted odds ratio, 0.30 [CI, 0.21 to 0.43]) during the influenza seasons. It was also associated with fewer outpatient visits for pneumonia and influenza and for all respiratory conditions. CONCLUSIONS: For elderly persons with chronic lung disease, influenza is associated with significant adverse health effects and influenza vaccination is associated with substantial health benefits, including fewer outpatient visits, fewer hospitalizations, and fewer deaths. Health care providers should take advantage of all opportunities to immunize these high-risk patients.

The health and economic benefits associated with pneumococcal vaccination of elderly persons with chronic lung disease.

BACKGROUND: More than 50% of the elderly population has not received pneumococcal vaccination. Uncertainty regarding the benefits of immunization, particularly for noninvasive disease, may contribute to the underuse of pneumococcal vaccine. OBJECTIVE: To assess the health and economic benefits associated with pneumococcal vaccination. METHODS: We conducted a 2-year retrospective cohort study among all elderly members of a staff-model managed care organization who had a baseline diagnosis of chronic lung disease. The study outcomes were assessed over 2 years, from November 15, 1993, through November 14, 1995, and included hospitalizations for pneumonia and influenza, death, and hospitalization costs. Using administrative data, we compared these outcomes for vaccinated and unvaccinated subjects using multivariate models to control for subjects' baseline demographic and health characteristics. The additive benefits of combined influenza and pneumococcal vaccination were also assessed for the 2 influenza seasons included in the study. RESULTS: There were 1898 subjects. Pneumococcal vaccination was associated with significantly lower risks for pneumonia hospitalizations (adjusted risk ratio [RR], 0.57; 95% confidence interval [CI], 0.38-0.84; P=.005) and for death (adjusted RR, 0.71; 95% CI, 0.56-0.91; P = .008). For the control outcome of all nonpneumonia hospitalizations, rates did not differ significantly between the 2 groups (adjusted RR, 0.91; 95% CI, 0.77-1.07; P= .24). During the influenza seasons included in the study, the benefits of pneumococcal and influenza vaccinations were additive, with an adjusted RR of 0.28 (95% CI, 0.14-0.58; P<.001) for the number of hospitalizations for pneumonia and influenza among persons who had received both vaccinations compared with those who had received neither and an adjusted odds ratio of 0.18 (95% CI, 0.11-0.31; P<.001) for death. Over the 2-year outcome period, pneumococcal vaccination was also associated with direct medical care cost savings. CONCLUSIONS: Pneumococcal vaccination of elderly persons with chronic lung disease was associated with fewer hospitalizations for pneumonia, fewer deaths, and direct medical care cost savings.

Genital human papillomavirus infection among male and female sex partners: prevalence and type-specific concordance.

Penile, cervical, and vulvovaginal samples from 50 couples attending a sexually transmitted disease clinic and perianal samples from women only were tested for human papillomavirus (HPV) DNA by dot filter hybridization (DFH) and polymerase chain reaction (PCR). Only 18% of women and 4% of men were HPV-positive by DFH, but 72% of women and 63% of men were HPV-positive by PCR. HPV type-specific concordance between partners was more common than predicted by chance (P = .01) and was associated with detection of HPV DNA by DFH in either partner. Thus, genital HPV infection in this population is common in both men and women, and the HPV type-specific concordance in sex partners is consistent with sexual transmission. Higher levels of genital or perianal HPV, as reflected by detection of HPV DNA with the less-sensitive DFH method, may promote sexual transmission.

Invasive Haemophilus influenzae infections in older children and adults in Seattle.

We recently saw two unusual manifestations of Haemophilus influenzae infection in adults in the Seattle area: fulminant sepsis in an otherwise-healthy man and three episodes of bacteremia in a woman with chronic liver disease. We retrospectively identified 79 bacteremic and 40 non-bacteremic cases of invasive H. influenzae infection developing in patients > or = 9 years of age between 1 January 1980 and 31 December 1990. The most common clinical presentations among patients with bacteremia included pneumonia (52%), septicemia (27%), meningitis (8%), gynecologic infection (5%), and epiglottitis (5%). Underlying illnesses were common in these patients, and overall mortality was 35.5%. Factors associated with mortality included underlying neurological disease, polymicrobial bacteremia, and advanced age. The clinical presentations of the 40 patients without bacteremia included soft-tissue abscesses (45%), lung abscesses (18%), peritonitis (13%), meningitis (8%), gynecologic infection (8%), epididymitis (5%), mastoiditis (3%), and osteomyelitis (3%). Thus H. influenzae disease has a variety of presentations and is associated with significant mortality in older children and adults. Further study is required to determine whether widespread administration of H. influenzae type b conjugate vaccine to infants will alter the development of subsequent disease in later life.

Dynamics of coagulase-negative staphylococcal colonization in patients and employees in a surgical intensive care unit.

Because there is little information about the frequency of carriage of various species of coagulase-negative staphylococci (CNS) in hospital staff, we prospectively investigated nasal CNS in patients and personnel in a Surgical Intensive Care Unit (SICU). The majority of CNS from personnel were Staphylococcus epidermiditis. The CNS species from patients on admission were more diverse and included multiply antibiotic-resistant S. haemolyticus. Patients' CNS became more like CNS colonizing personnel after admission with respect to both antimicrobial susceptibility and speciation. Plasmid and antibiotic sensitivity profiles of S. epidermidis resistant to multiple antibiotics from five patients were identified as those from one employee, but there was no evidence that this was of clinical significance. A variety of factors influence nasal colonization by CNS in SICUs. The nasal CNS of patients change after admission and may become more resistant and less diverse. The factors influencing changes in the antibiotic susceptibility and the aetiology of CNS infection require further study.

High-output heart failure due to hepatic arteriovenous fistula during pregnancy: a case report.

A 32-year-old multiparous gravida presented at 38 weeks' gestation with a second pregnancy complicated by congestive heart failure. Through noninvasive testing, hepatic arteriovenous malformation was diagnosed as the etiologic factor. This has not been reported as a cause of heart failure in pregnancy, although arteriovenous malformations in other organs have been associated with this complication.