Survival in commercially insured multiple sclerosis patients and comparator subjects in the U.S.

OBJECTIVE: Compare survival in patients with multiple sclerosis (MS) from a U.S. commercial health insurance database with a matched cohort of non-MS subjects. METHODS: 30,402 MS patients and 89,818 non-MS subjects (comparators) in the OptumInsight Research (OIR) database from 1996 to 2009 were included. An MS diagnosis required at least 3 consecutive months of database reporting, with two or more ICD-9 codes of 340 at least 30 days apart, or the combination of 1 ICD-9-340 code and at least 1 MS disease-modifying treatment (DMT) code. Comparators required the absence of ICD-9-340 and DMT codes throughout database reporting. Up to three comparators were matched to each patient for: age in the year of the first relevant code (index year - at least 3 months of reporting in that year were required); sex; region of residence in the index year. Deaths were ascertained from the National Death Index and the Social Security Administration Death Master File. Subjects not identified as deceased were assumed to be alive through the end of 2009. RESULTS: Annual mortality rates were 899/100,000 among MS patients and 446/100,000 among comparators. Standardized mortality ratios compared to the U.S. population were 1.70 and 0.80, respectively. Kaplan-Meier analysis yielded a median survival from birth that was 6 years lower among MS patients than among comparators. CONCLUSIONS: The results show, for the first time in a U.S. population, a survival disadvantage for contemporary MS patients compared to non-MS subjects from the same healthcare system. The 6-year decrement in lifespan parallels a recent report from British Columbia.

Relationship between infant sleep position and motor development in preterm infants.

To determine whether motor development in premature infants varies according to sleep position, we evaluated 213 infants <1750 g birth weight enrolled in the Collaborative Home Infant Monitoring Evaluation (CHIME). At 56 weeks postconceptional age (PCA), sleep position was determined by maternal report, and the Bayley Scales of Infant Development 2nd Edition (BSID-II) were performed. Infants who slept supine were less likely than infants who slept prone to receive credit for maintaining the head elevated to 45 degrees (p = .021), and infants who slept nonprone were less likely than prone sleepers to receive credit for maintaining the head elevated to 90 degrees and lowering with control (p = .001). The Psychomotor and Mental Development Indices at 56 and 92 weeks PCA were not altered by usual sleep position at 56 weeks PCA. In summary, infants sleeping supine are less able to lift the head and lower with control at 56 weeks PCA, but global developmental status was unaffected. Supine sleeping has been associated with decreased risk for sudden infant death syndrome, but compensatory strategies while awake may be needed to avoid delayed acquisition of head control.

Telephone subsidy: an effective incentive for successful participation in home memory monitor study.

CONTEXT: The Collaborative Home Infant Monitoring Evaluation (CHIME) study enrolled healthy term infants and 3 groups of infants considered to be at increased risk for sudden infant death syndrome to evaluate apnea and bradycardia events in the home. Mother-infant pairs without a telephone were ineligible for enrollment. OBJECTIVE: To determine whether mother-infant pairs who were offered a telephone subsidy would agree to enroll in CHIME and achieve protocol compliance rates comparable with those of matched subjects able to afford telephones. DESIGN: Thirty-one telephone subsidy subjects were retrospectively compared with 55 control subjects matched for study group, site, birth weight, and maternal race, age, and education. SETTING: Collaborative Home Infant Monitoring Evaluation clinical research centers in Honolulu, Hawaii, and Toledo, Ohio. INTERVENTION: Provision of telephone subsidy to otherwise eligible enrollees for CHIME. MAIN OUTCOME MEASURES: Frequency of compliance with protocol requirements for follow-up evaluations and for extent of home monitoring. RESULTS: Subsidy subjects achieved protocol completion rates that were comparable with those of control subjects, for developmental assessments at 56 and 92 weeks postconceptional age (PCA), and for the polysomnogram. Unexpectedly, however, subsidy subjects were more likely to have a developmental assessment at 44 weeks PCA (P =.02), as well as a cry analysis (P =.04). They were also more likely to use the CHIME home monitor for more hours during weeks 2 through 5 (P =.004), have a higher percentage using the monitor for 10 or more hours per week during weeks 2 through 5 (P =.009), and have a higher total number of days of monitor use throughout 6 months (P <.001). Mean cost of the subsidy was $3.25 per day of monitor use, and monitor use per day was directly related to total cost of the subsidy (P =.02). CONCLUSIONS: Telephone subsidy is an effective financial incentive. At least within the context of the CHIME study, telephone subsidy enhanced access to health care, and in some categories it resulted in enhanced protocol compliance.

Newborn acoustic cry characteristics of infants subsequently dying of sudden infant death syndrome.

OBJECTIVE: To test the hypothesis that the occurrence of a neonatal cry exhibiting a high first formant is a risk factor for sudden infant death syndrome (SIDS) and to evaluate the association between SIDS and other acoustic cry variables. METHOD: We recorded cries and obtained medical and demographic data for 21,880 apparently healthy term newborns. Two cries were recorded between days 2 and 7 of life, after a painful stimulus at the time of routine blood drawing. Acoustic variables were measured with an automated computer-based analysis system. Twelve infants died of SIDS. Age at death ranged from 19 days to 6.5 months. Autopsies were performed in all cases. At least one cry was analyzed for all 12 infants who died of SIDS and 20,167 infants without SIDS. Two cries were analyzed for 9 infants who died of SIDS and 14,235 infants without SIDS. RESULTS: Newborns whose first cries exhibited a high first formant were more likely to die of SIDS than infants whose first cries did not have this characteristic (relative risk, 3.5; 95% confidence interval [CI], 1.1 to 12). The relative risk for SIDS increased to 8.8 (95% CI, 2.2 to 35) for newborns whose second cries showed that this characteristic persisted. Newborns with the combination of both a high first formant and a high number of mode changes on both of two cries had a relative risk of 32 (95% CI, 8.7 to 120). CONCLUSIONS: We have shown an association between alterations in neonatal cry acoustics and SIDS. Cry analysis represents a potentially important research tool that, when studied in relation to other physiologic measures, may lead to an improved understanding of SIDS.

Effects of in utero cocaine exposure on newborn acoustical cry characteristics.

As part of a large, multicenter study of newborn cry analysis and Sudden Infant Death Syndrome, we examined the effects of in utero cocaine exposure on ten acoustical cry characteristics. Newborn cry recording and medical record review was performed for 23,948 newborns. Cocaine use during pregnancy (determined by record review) was identified in 438 (1.8%) women (310 by self-report only; 128 newborns also had positive urine assay). A demographically similar group of 373 newborns, selected from the 23,510 newborns without known cocaine exposure, made up the comparison group. Cry analysis was technically possible for 768 recordings: 404 cocaine-exposed and 364 non-exposed controls. Comparison of cocaine-exposed vs control newborns, after adjustment for potential confounding variables, found significant differences including: fewer cry utterances (P = .001), more short cries (P = .02), and less crying in the hyperphonation mode (P = .01), for the cocaine-exposed neonates. As reported in other studies, cocaine-exposed newborns also were significantly lower in birth weight, length, and head circumference. Newborns who had positive urine tests for cocaine suffered the greatest effects on both cry and growth parameters. These findings suggest a pattern of underaroused neurobehavioral function and are consistent with the emerging picture of the adverse neurobehavioral effects of cocaine. Developmental outcome studies are in progress to determine if acoustical analysis of the newborn cry can be used to identify cocaine-exposed newborns who are at highest risk for poor outcome.

Neurobehavioral syndromes in cocaine-exposed newborn infants.

The effects of fetal cocaine exposure on newborn cry characteristics were studied in 80 cocaine-exposed and 80 control infants. The groups were stratified to be similar on maternal demographic characteristics and maternal use of other illegal substances and alcohol during pregnancy. The hypothesis was that excitable cry characteristics were related to the direct effects of cocaine, while depressed cry characteristics were related to the indirect effects of cocaine secondary to low birthweight. Structural equation modeling (EQS) showed direct effects of cocaine on cries with a longer duration, higher fundamental frequency, and a higher and more variable first formant frequency. Indirect effects of cocaine secondary to low birthweight resulted in cries with a longer latency, fewer utterances, lower amplitude, and more dysphonation. Cocaine-exposed infants had a lower birthweight, shorter length, and smaller head circumference than the unexposed controls. Findings were consistent with the notion that 2 neurobehavioral syndromes, excitable and depressed, can be described in cocaine-exposed infants, and that these 2 syndromes are due, respectively, to direct neurotoxic effects and indirect effects secondary to intrauterine growth retardation.

Spectral characteristics of sound transmission in the human respiratory system.

The amplitude of sound transmission from the mouth to a site overlying the extrathoracic trachea and two sites on the right posterior chest wall over the 100-600 Hz frequency range was measured in eight healthy adult subjects. An acoustic driver and a rigid tube were employed to introduce sound into the mouths of the subjects at resting lung volume, and the transmission measurements were performed using lightweight accelerometers. Similar spectral characteristics of acceleration were observed in all of the subjects showing peaks in the transmission. These characteristics included 1) two regions of increased transmission over the frequency range of the measurements, 2) a decrease in the magnitude of acceleration of the chest wall as compared to the tracheal site of roughly 20 dB at lower frequencies, 3) a strong trend of decreasing acceleration of the chest wall with increasing frequency. These spectra agreed favorably with the predictions of a theoretical model of the acoustical properties of the respiratory system. The model suggests the primary structural determinants of a number of the observed characteristics including the importance of the lung parenchyma in sound attenuation.

A model of acoustic transmission in the respiratory system.

A theoretical model of sound transmission from within the respiratory tract to the chest wall due to the motion of the walls of the large airways was developed. The vocal tract, trachea, and the first five bronchial generations are represented over the frequency range from 100 to 600 Hz by an equivalent acoustic circuit. This circuit allows the estimation of the magnitude of airway wall motion in response to an acoustic perturbation at the mouth. The radiation of sound through the surrounding lung parenchyma is represented as a cylindrical wave in a homogeneous mixture of air bubbles in water. The effect of thermal losses associated with the polytropic compressions and expansions of these bubbles by the acoustic wave is included and the chest wall is represented as a massive boundary to the wave propagation. The model estimates the magnitude of acceleration over the extrathoracic trachea and at three locations on the posterior chest wall in the same vertical plane. The predicted spectral characteristics of transmission are consistent with previous experimental observations. This theoretical approach suggests that the locations of the spectral peaks are a strong function of the geometry and the wall properties of the airways, while the attenuation at higher frequencies is primarily associated with the absorption of sound in the parenchyma.

Pneumograms in infants who subsequently died of sudden infant death syndrome.

Victims of sudden infant death syndrome (SIDS) have occasionally been reported to have had prolonged apnea or an increased frequency of short apnea prior to their deaths. To examine the extent of these abnormalities, we compared pneumograms obtained in 17 infants who subsequently died of SIDS (10 with history of apnea) with those of 34 age- and sex-matched controls. The recordings were analyzed by a computer program that avoided observer bias. SIDS infants had significantly greater mean heart rate (P less than 0.05) and periodic breathing during quiet time (P less than 0.003) than control infants had. The apnea in SIDS infants tended to be more periodic than in control infants (P less than 0.002). In addition, the incidence of bradycardia was greater in SIDS (three infants) than in controls (none) (P less than 0.03). These differences suggest a disturbance of autonomic function prior to death in some victims of SIDS.

Infant cry: a clue to diagnosis.

It has been postulated that the infant cry is a reflection of complex neurophysiologic functions and that analysis of the infant cry can be utilized to assess the infant's status. To test this hypothesis a model of cry production was developed utilizing a computer-based signal processing system that enabled the observer to relate closely the acoustic properties of the cry to the anatomic and physiologic characteristics of the infant producing the cry. The cries of 87 infants were analyzed following a standardized pain stimulus. Cry features were grouped into eight evaluative tests. Only seven of 55 apparently normal term infants had the abnormality "glottal instability" whereas 11 of 12 infants with bilirubin values in the 10 to 20 mg/100 ml range displayed the glottal instability pattern. An additional group of 17 infants with a variety of problems was studied; 14 of 17 displayed two or more abnormalities, and ten of 12 infants with respiratory disease had a unique pattern. Of particular interest was the finding of acoustical features suggestive of a constriction in the vocal tract in three infants; two of these infants were studied prospectively and subsequently were victims of sudden infant death syndrome and the third had a sibling with recurrent apnea. These results suggest that the analysis of the infant cry holds promise for detecting a number of abnormalities and may prove valuable as screening test to detect infants at risk for sudden infant death syndrome.