DNA-directed cell-free protein-synthesizing system of Bacillus subtilis.

A cell-free coupled system of transcription and translation using cell extracts from Bacillus subtilis and DNA from phage SP82 has been developed. Under optimum conditions, it incorporated approx. 300 pmol methionine during a 1 h incubation. The activity of the system increased linearly as the concentration of S-150 supernatant fraction protein increased from 125 to 325 microgram per assay. The optimum Mg2+ concentration was 12.5-15 mM. Ribosomes required treatment with DNAase in order to reduce endogenous activity, but the S-150 fraction was kept DNAase-free to prevent degradation of exogenously added DNA. The coupled system was sensitive to inhibitors of RNA and protein synthesis. Kinetic studies showed that the number of pmol of nucleotides present in newly synthesized RNA increased linearly for the first 20-min reaction and that the rate of amino acid incorporation increased linearly for the first 30 min. Polyacrylamide gel electrophoresis of the in vitro synthesized products yielded a band pattern that closely resembled the pattern of early phage SP82 proteins produced in vivo.

Operational criteria for adverse drug reactions in evaluating suspected toxicity of a popular scabicide.

A recently developed algorithm for the diagnosis of adverse drug reaction (ADR) was used to investigate the quality of evidence in reported cases of ADRs to 1% gamma benzene hexachloride (GBH), a popular scabicide and pediculicide currently under suspicion as a cause of central nervous system (CNS) toxicity, especially in children. Of the 53 reported cases of alleged toxicity, 37 were associated with lindane insecticide (greater than 1% GBH), which is not a pharmaceutical preparation. Of these 37 cases, 34 scored as definite or probable reactions on the algorithm. Of the 26 reports associated with the drug, 1% GBH, none scored as definite and only 6 as probable ADRs. Of these 6 probable cases, 5 represented inappropriate application or unintended ingestion. The use of rigorous operational criteria, such as those developed in this algorithm, permits a scientifically disciplined assessment of whether or not a drug has been fairly indicted, and also provides valuable clinical information about other aspects of suspected drug toxicity.

Have there been changes in the epidemiology of sexual abuse of children during the 20th century?

Have there been changes in the epidemiology of sexual abuse of children during the 20th century? To explore this question, a comparison was made between the results of the survey conducted by Alfred Kinsey and colleagues in the 1940s of women in the United States, the majority of whom were born between 1900 and 1929, and the results of more recent studies of the epidemiology of sexual abuse. In Kinsey's study, 24% of 4,441 women reported at least one episode of sexual abuse before adolescence; in 49% of the episodes, the perpetrator was not known to the child and, in 50%, the abuse did not involve bodily contact. These findings are compared to the results of more recent epidemiologic surveys, particularly Russell's study conducted in San Francisco in 1978. Although there are important differences in the methodologies used by Kinsey and Russell, it is likely that changes have occurred in the prevalence and nature of sexual abuse in the 20th century. Russell described a higher prevalence of sexual abuse, a greater proportion of perpetrators who were relatives or adults known to the child, and a greater proportion of serious types of sexual abuse.

Risk factors for child abuse: methodologic standards in case-control studies.

To determine whether the findings of case-control studies of risk factors for child abuse may have been biased because of inattention to scientific principles of research design, 22-case-control studies were reviewed investigating either of two risk factors: (1) prematurity or low birth weight of the abused child or (2) young maternal age of the mother of the abused child. Each study was examined to determine compliance with seven methodologic standards that would minimize bias or distortion of the results. No study satisfied all seven standards. Two standards, choice of a specific control group and adjustment for differences in clinical and demographic susceptibility factors, most often affected the results. Studies complying with both of these standards indicated that prematurity or low birth weight is not a risk factor for abuse and that young maternal age at the birth of the abused child is likely to be a risk factor. Few studies complied with the standard concerned with avoidance of detection bias; this failure may have a major effect on the direction bias; this failure may have a major effect on the direction of the results of certain studies. Previous case-control studies of child abuse have important methodologic flaws that can affect the validity of the results. The standards presented should be helpful in planning methodologically rigorous studies.

Marital adjustment to chronic childhood illness: a critique of the literature.

Thirty-four studies of marital adjustment were selected from the literature on family adjustment to chronic childhood illness. Studies were reviewed to determine whether divorce rates were elevated or marital adjustment was poorer compared with that of families of healthy children. Of 23 studies reporting divorce rates, only six used a group of families without a chronically ill child for comparison. These studies showed no significant differences in the divorce rates between groups. Of 23 studies of marital adjustment, 83% investigated marital distress. Four of seven studies with comparison groups showed that marital distress was increased in parents of chronically ill children. Other areas of marital adjustment, such as communication, decision-making, and role flexibility, have received almost no attention by researchers. It is questioned whether divorce or distress is an adequate indicator of marital adjustment in general. Further studies are needed to understand the relationships between divorce, distress, and other important areas of marital adjustment to chronic childhood illness.

Is intrauterine growth retardation a risk factor for child abuse?

A case-control study was conducted to determine whether infants with intrauterine growth retardation are at an increased risk of child abuse. Case children were those who had been born at Yale-New Haven Hospital and were reported to the hospital's child abuse committee because they had been physically abused. For each case, one control child was chosen from the hospital's log of births and matched to the case child by age, gender, race of the mother, method of payment for the hospitalization, and the provider of the child's health care at the time of birth. Infants were defined as having intrauterine growth retardation if they had either a ponderal index or a birth weight that was less than the tenth percentile for gestational age using the Kansas City or Denver growth standards. We identified 117 case-control pairs that met those criteria. The matched odds ratios for each of the four definitions of intrauterine growth retardation were less than one, indicating that infants with intrauterine growth retardation are at a decreased risk of abuse. The matched odds ratio for a low ponderal index according to the Kansas City standard was 0.4 (95% confidence interval 0.19, 0.83). This result was not affected by such possible confounding factors as the mother's age. We conclude that infants with intrauterine growth retardation are not at an increased risk and may be at a decreased risk of physical abuse.

Evaluating intensive family preservation programs: a methodological review.

OBJECTIVES: To determine the adequacy of evaluations of family preservation services (FPS), which are designed to support families and prevent out-of-home placements of children at risk of abuse or neglect, and to assess the effectiveness of FPS at reducing out-of-home placements of children. DATA SOURCES: References published from 1977 to 1993 were identified from a computerized search of databases for English-language publications using the key phrases "family preservation," "child abuse," and "family-based services." Unpublished references were identified by mail or phone from a listing of more than 200 programs in a national directory. SELECTION OF STUDIES: Of 802 references initially identified, 46 program evaluations were reviewed. Ten studies met the following inclusion criteria: (1) evaluated an intensive family preservation program, (2) included outcome data in the report, and (3) used a comparison group. Five were randomized trials, and 5 were quasi-experimental studies (nonrandomized). DATA EXTRACTION: Descriptive information about the programs and evaluations was collected. To determine methodological quality, two independent raters used a 15-item questionnaire to examine the assignment of families to treatment groups, the interventions provided, and the outcomes assessed. A composite score of 11 or greater represented an acceptable study, 6 to 10 represented an adequate study, and 5 or less represented an unacceptable study. RESULTS: Only two studies were rated acceptable, four were adequate, and four were unacceptable. Methodological shortcomings included poorly defined assessment of risk, inadequate descriptions of the interventions provided, and nonblinded determination of the outcomes. Rates of out-of-home placements were 21% to 59% among families who received FPS and 20% to 50% among comparison families. The relative risk of placement was significantly reduced by FPS in only two studies (one randomized trial and one quasi-experimental study). CONCLUSIONS: Despite current widespread use of FPS to prevent out-of-home placements of children, evaluations of FPS are methodologically difficult and show no benefit in reducing rates of out-of-home placements of children at risk of abuse or neglect in 8 of 10 studies. Consistent, methodologically rigorous evaluations are needed to determine the effectiveness of FPS and to guide social policy for high-risk children and their families.

Prolonged continuous monitoring of intracranial pressure in severe Reye's syndrome.

Evidence from both clinical and pathological investigations suggests that increased intracranial pressure (ICP) is a significant factor in the mortality of patients with Reye's syndrome. This, coupled with a critical review of our previous 22 patients, which failed to document the efficacy of exchange transfusion, led us to include continous ventricular pressure monitoring in the supportive care of children with Reye's syndrome. To date, three children, ages 3 to 5 years, have been managed with continuous ICP monitoring. All had stage IV coma by both clinical and electroencephalographic criteria. Peak blood ammonia concentrations were 1,036, 316, and 56micronug/100 ml; all had elevations of serum glutamic oxaloacetic transaminase level, prothrombin time, and creatine phosphokinase level as well. Rapid, unprediatble increases in ICP occurred for many days in all children. Therapeutic measures most successful in controlling ICP were the intravenous administration of mannitol and hyperventilation. Elevations in ICP occurred despite serum osmolality as high as 418 mOsm and following oral administration of glycerol. Rapid increases in ICP also resulted from routine manipulation of the patients (e.g., postural drainage). Exchange transfusion, used in two of the three patients, increased ICP in one child and had no effect in the other. All three children have achieved complete recovery and are doing well 6 months after their illness. Our experience with these children suggests that vigorous supportive therapy, including careful monitoring of ICP, should be used as a basis of comparison when evaluating claims of specific treatment in Reye's syndrome.

Long-bone fractures in young children: distinguishing accidental injuries from child abuse.

While testifying in child abuse cases, physicians have been frustrated by the lawyer who asks, "Doctor, how did this injury happen?" The medical records and radiographs of 215 children younger than the age of 3 with fractures evaluated by a pediatric service during a 5-year period were retrospectively reviewed in an attempt to elucidate the mechanism of childhood fractures. Based on these reviews, two clinicians and two pediatric radiologists rated the likelihood that the fracture was either accidental or due to child abuse. Long-bone fractures were strongly associated with abuse. This report focuses on the 39 children with either humeral or femoral fractures. Fourteen children had humerus fractures. Eleven were considered to be the result of child abuse, and 3 the result of accidents. The latter 3 were supracondylar elbow fractures in children who fell from a tricycle, a rocking horse, or downstairs. Humerus fractures other than supracondylar fractures were all found to be due to abuse. There were 25 femur fractures. Nine were found to be from abuse, 14 were found to be from accidents, and 2 could not be rated. Sixty percent of femur fractions in infants younger than 1 year of age were due to abuse. Although it is taught that femur fractures in young children are inflicted unless proven otherwise, in this study it was found that femur fractures often are accidental and that the femur can be fractured when the running child trips and falls.

Does breast-feeding protect against infections in infants less than 3 months of age?

To determine whether breast-feeding protects infants from infections, a case-control study was conducted. The cases were previously healthy children who were admitted to Yale-New Haven Hospital for an infectious illness at or before 90 days of age. The controls were chosen from the log of births and matched to the cases for five important demographic variables. In addition, logistic regression models were used to adjust the results for other potential confounders. To minimize the potential surveillance bias that might occur if formula-fed and breast-fed infants with the same degree of illness have a different probability of being hospitalized, the case-control pairs were stratified by the severity of the medical condition of the case at the time of hospitalization. For the 281 case-control pairs, the matched odds ratio was .50 (95% confidence interval .32, .77; P less than .005), which indicates that breast-feeding is protective against infections. However, this apparent protective effect was diminished substantially when the data were stratified according to the severity of illness: the matched odds ratio for the 164 infants with serious illnesses was .79 (.47, 1.32; P less than .50), and for the 117 infants with mild illnesses it was .17 (.03, .44; P less than .001). These stratified results suggest that breast-feeding protects infants from hospitalization rather than from infections. Failure to consider the problem of surveillance bias may lead to erroneous conclusions about the protective effect of breast-feeding.

Psychological sequelae of medical complications during pregnancy.

To determine whether mothers with complicated pregnancies are at increased risk of postpartum depression and whether their children are at increased risk of being perceived as vulnerable, the investigators conducted an interview survey of mothers of 1095 children aged 4 to 8 in a community-based sample of primary care pediatric practices. The offspring were viewed as vulnerable by 17% of the women with severe pregnancy complications and 9% of the women without pregnancy complications (relative risk = 1.88; 95% confidence interval = 1.11, 2.63). Women with a severe complication of pregnancy were significantly more likely to report postpartum depression than those without a complication (27% vs 11%; relative risk = 2.45; 95% confidence interval = 1.55, 3.01). These relationships persisted after adjustment for prematurity, neonatal hospitalization, and demographic factors. It is concluded that pregnancy complications may place a woman at increased risk of postpartum depression and may have important effects on a mother's long-term perceptions of her child's vulnerability to illness.

Are children born to young mothers at increased risk of maltreatment?

Previous case-control or cross-sectional studies have provided conflicting results about whether children of teenage mothers are at increased risk of maltreatment compared with children of older mothers. This study is the first to examine this question using a longitudinal, cohort design and the first to address important methodologic issues such as detection bias. Subjects were 219 consecutive index children born to inner-city women who were 18 years or younger and 219 sociodemographically similar comparison children born to women 19 years or older. Data were collected by reviewing the medical records of each child through the fifth birthday. Three outcomes were examined: maltreatment, poor growth, and a change in the child's primary caretaker. Maltreatment was ascertained by having two experts, one of whom was blind to the group status, review each injury documented in the records. Predefined criteria were used to distinguish unintentional injuries from maltreatment (abuse, neglect, or sexual abuse). Maltreatment occurred more frequently in the children of young mothers (12.8%) than in the comparison group (6.4%) (risk ratio [RR] = 2.00; 95% confidence interval [CI] = 1.17, 3.64). Poor growth, defined by growth criteria, occurred in 6.9% of the index group and in 4.1% of comparison children (RR = 1.67; 95% CI = 0.75, 3.73). A change in the child's primary caretaker, either because of placement in foster care or because the mother left the home, occurred in 12.8% of the index group and in 3.2% in comparison children (RR = 4.00; 95% CI = 1.80, 8.87).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of health services by children who were identified during the postpartum period as being at high risk of child abuse or neglect.

OBJECTIVE: To examine the rates of hospitalizations of children identified as beingat high risk of maltreatment compared with a sociodemographically similar comparison group. DESIGN: retrospective study comparing a high-risk cohort with a sociodemographically matched comparison group at Yale-New Haven Hospital (New Haven, CT). PATIENTS: One huntred fourteen children who were identified from January 1979 through December 1981 by clinicians on the postpartum ward as being at high risk of abuse or neglect and 114 sociodemographically similar comparison children who were matched according to date of birth, race, gender, and method of payment for the hospitalization. MAIN OUTCOME MEASURER: During the first 4 years of life, the number of hospitalizations, reasons for admissions, and appropriateness of days in the hospital using the Pediatric Appropriateness Evaluation Protocol. RESULTS: Significantly more high-risk children wer hospitalized (40% vs 22%; risk ratio 1.84; 95% confidence interval, 1.23-2.74). High-risk children were hospitalized for 649 (mean, 9.0) days versus 124 (mean, 3.8) days in comparison children. For admissions for medical problems, 28% of hospital days in the high-risk group were considered inappropriate by the Pediatric Appropriateness Evaluation Protocol versus 8% in the comparison group. CONCLUSIONS: There are substantial differences in the rates of hospitalizations, lengths of stay, and appropriateness of days in children identified as being at hish risk of maltreatment compared with a sociodemographically similar, non-high-risk group. Preventive programs that are aimed at reducing rates of child maltreatment in high-risk young children also should examine the program's effects on the use of hospital care.

Identification and management of psychosocial and developmental problems in community-based, primary care pediatric practices.

The importance of psychological and social issues for children's well-being has long been recognized and their importance in the practice of pediatrics is well documented. However, many of the studies looking at this issue have emphasized psychiatric problems rather than issues commonly referred to as the new morbidity. The goal of this research was to refocus interest on the problems of the new morbidity. This study examined the rates and predictors of psychological problems in 19 of 23 randomly chosen pediatric practices in the greater New Haven area. Families of all 4- to 8-year-old children were invited to participate and to complete the Child Behavior Checklist prior to seeing a clinician. Clinicians completed a 13-category checklist of psychosocial and developmental problems based on a World Health Organization-sponsored primary care, child-oriented classification system. Of the 2006 eligible families, 1886 (94%) participated. Clinicians identified at least one psychosocial or developmental problems in 515 children (27.3%). Thirty-one percent of the children with problems received no active intervention, 40% received intervention by the clinician, and 16% were referred to specialty services. Not surprisingly, children whose problems were rated as moderate or severe were twice as likely to be referred compared with children with mild problems. Recognition of a problem was related to four characteristics: if the visit was for well child rather than acute care; if the clinician felt he or she knew a child well; if the child was male; and if the child had unmarried parents (all P less than or equal to .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anatomically correct dolls used in interviews of young children suspected of having been sexually abused.

To determine the value of using anatomically correct dolls in diagnostic interviews of young children suspected of being sexually abused, the records of 83 children who were less than 7 years of age and who were evaluated at Yale-New Haven Hospital because of a suspicion of sexual abuse were reviewed. The dolls were used in 60 cases (72%). When the dolls were used, children provided significantly more information than by interview alone about what had happened and about the identity of the suspected perpetrator. Children less than 3 years of age, however, were unable to provide details about the abuse despite the use of the dolls. The ratings of the likelihood that sexual abuse had occurred were based on all of the information in the case including that obtained through the diagnostic interview with the dolls. When these ratings were compared with the ratings based on evidence obtained solely from noninterview data, the likelihood of abuse was higher in 35% of the cases. It was concluded that substantially more information is provided by young children when anatomically correct dolls are used and that the likelihood of detection of abuse is increased when information from the child is included in the assessment.

Does quality of care affect rates of hospitalization for childhood asthma?

BACKGROUND: Hospitalization rates for childhood asthma are three times as high in Boston, Massachusetts, as in Rochester, New York; New Haven, Connecticut, rates are intermediate. We undertook this study to determine how care for children admitted for asthma varies across these communities. METHODS: We performed a community-wide retrospective chart review. We reviewed a random sample of all asthma hospitalizations, from 1988 to 1990, of children 2 to 12 years old living in these communities (n = 614). Abstracted data included demographics, illness severity, and treatment before admission. RESULTS: Compared with Rochester children, Boston children were less likely to have received maintenance preventive therapy (inhaled corticosteroids or cromolyn [odds ratio (OR), 0.4 (0.2, 0.9)]), acute "rescue" therapy (oral corticosteroids [OR, 0.2 (0.1, 0.4)]), or inhaled beta-agonist therapy [OR, 0.5 (0.3, 1.0)]. A larger proportion of admitted asthmatic patients in Boston (34%) were in the least severely ill group-oxygen saturation 95% or above-compared with patients in Rochester (20%). CONCLUSIONS: The quality of ambulatory care, including choice of preventive therapies and thresholds for admission, likely plays a key role in determining community hospitalization rates for chronic conditions such as childhood asthma.

Relationship between infant feeding and infectious illness: a prospective study of infants during the first year of life.

Prior studies investigating the relationship between infant feeding and infectious illnesses in developed countries have provided conflicting data about whether breast-feeding protects against common infectious illnesses early in life. These conflicts may in part be due to the failure to consider the following methodologic issues: (1) collecting data prospectively at frequent intervals for active surveillance of the detection of infections and of feeding practices, (2) specifying what is meant by infectious illnesses and breast-feeding, (3) controlling for confounding variables such as social class or presence of siblings in the household, and (4) applying appropriate analytical strategies to a population in which both feeding and exposure to illness change over time. A total of 500 infants born consecutively in a university-affiliated community hospital in Copenhagen, Denmark, were studied prospectively for the first 12 months of life by means of a detailed, monthly, mailed questionnaire that focused on feeding practices and illnesses (overall response rate, 73%). The percentage of infants who were completely or mostly breast-fed decreased from 88% at 1 month to 20% at 12 months of age. After adjustment for major covariates, no statistically significant relationship was found between the type of infant feeding and the incidence of four categories of infectious illnesses: gastroenteritis, upper respiratory illness, otitis media, and lower respiratory illness. The adjusted incidence density ratio for gastroenteritis was 1.067 (95% confidence interval = 0.982, 1.226) and for upper respiratory illnesses 0.984 (95% confidence interval = 0.883, 1.096).(ABSTRACT TRUNCATED AT 250 WORDS)

Educational intervention by computer in childhood asthma: a randomized clinical trial testing the use of a new teaching intervention in childhood asthma.

To affect asthma-related knowledge, behavior, and morbidity, researchers tested a new educational intervention for children with asthma: an asthma-specific computer game called Asthma Command, which was specifically designed for this study. Sixty-five children with moderately severe asthma were randomly assigned to one of two groups, and 54 completed the study. Both groups were seen approximately six times during the 1 year of the study. Control subjects (n = 29) played routine computer games. Experimental subjects (n = 25) played Asthma Command. Compared with children in the control group, experimental subjects showed improvement in knowledge about asthma (P less than .001), behavior related to the management of asthma (P less than .008), and a trend toward the reduction of acute visits due to asthma (P less than .13). Children in the experimental group also scored higher on the assessment of behaviors related to the management of asthma that were specifically addressed by the intervention provided by Asthma Command (P less than .01). Differences between the control and experimental groups showed a greater improvement in the experimental group in 21 (84%) of the 25 outcome variables in the study (P = .004, Sign test). The study indicates that an asthma-specific computer game can significantly affect knowledge and behavior and may potentially affect morbidity in childhood asthma.

Identification of psychosocial problems in pediatric primary care: do family attitudes make a difference?

OBJECTIVE: To evaluate the affect of families' attitudes about the appropriateness of discussing psychosocial concerns on pediatric providers' identification of psychosocial problems. DESIGN: These data were collected as part of the Greater New Haven Child Health Study, New Haven, Conn. The study design was a prospective cohort. SETTING: Families were recruited from a stratified random sample of all primary care practices in the greater New Haven area. Nineteen of 23 invited practices agreed to participate including 2 prepaid practices, 2 neighborhood health centers, and 7 fee-for-service group and 8 fee-for-service solo practices. PARTICIPANTS: All families of children aged 4 to 8 years who attended these practices during 2 separate 3-week periods (1 in fall 1987 and 1 in spring 1988) were invited to participate in the study. Families were invited to participate only once, on the first contact with any eligible child, using approved procedures. Of 2006 eligible families, 1886 (94%) chose to participate. MAIN OUTCOME MEASURE: The outcome variable for these analyses is the identification of any behavioral, emotional, or developmental problem by the pediatrician on the 13-category checklist. Overall, pediatric clinicians identified 27.5% of children with 1 or more psychosocial problems. RESULTS: Our data suggest that there is a great deal of discrepancy between what parents report is appropriate to do when their children have psychosocial problems and what they actually do when they recognize such problems in their children. Most (81.1%) believed it was appropriate to discuss 4 or more of the 6 hypothetical situations with their children's physician, while only 40.9% actually did discuss any of these problems with a physician when a problem occurred. Given the correlates of parents who intended to discuss such problems (higher education, older age, Euro-American ethnicity, higher income, married, availability of medical insurance) the possibility that parents are providing socially acceptable responses to such questions seems likely. Further, our data indicate that parents' actual reports of discussions of psychosocial problems is unrelated to whether physicians identified those problems in children. CONCLUSIONS: Pediatricians'judgments about the presence of psychosocial problems in their young patients seem to be based on their own observations rather than on what parents report. Physician-parent communication about psychosocial problems will be increasingly important as primary care physicians assume their role as gatekeepers to more expensive services such as mental health interventions.

Health care and hospitalizations of young children born to cocaine-using women.

OBJECTIVES: To examine the health care and hospitalizations of young children (birth to age 2 years) born to cocaine-using women and to assess the extent to which premature births account for differences between these children and comparison children. DESIGN: A retrospective cohort design using a repeat-matching method: comparison children were matched to subjects with exposure to cocaine on 6 sociodemographic variables, first, without attention to gestational age and then using the gestational age as additional matching variable. SETTING: City hospitals and primary care clinics. SUBJECTS: Children of women giving birth at a single hospital. MAIN OUTCOME MEASURES: Hospital admission and indexes of health care use for children from birth to age 2 years. RESULTS: Of the 139 subjects with exposure to cocaine, 23% were born prematurely compared with only 6% in the first comparison ( P < .001). At birth, children with exposure to cocaine remained in the hospital longer (P < .01), but this difference was explained by the increased prevalence of prematurity. By age 2 years, these children had significantly fewer visits for health care maintenance (P < .001), were less likely to have completed immunizations (P < .05), and spend more days in the hospital than comparison children. These differences were not related to prematurity, but were explained by differences in sociodemographic characteristics. CONCLUSION: Although prematurity is the major reason for lengthier hospital stays at birth of children with exposure to cocaine, adverse social factors contribute most to inadequate preventive health care and increased stays in the hospital in subsequent years.