Disruptive mood dysregulation disorder at the age of 6 years and clinical and functional outcomes 3 years later.

BACKGROUND: Little is known about the predictive validity of disruptive mood dysregulation disorder (DMDD). This longitudinal, community-based study examined associations of DMDD at the age of 6 years with psychiatric disorders, functional impairment, peer functioning and service use at the age of 9 years. METHOD: A total of 473 children were assessed at the ages of 6 and 9 years. Child psychopathology and functional impairment were assessed at the age of 6 years with the Preschool Age Psychiatric Assessment with parents and at the age of 9 years with the Kiddie-Schedule of Affective Disorders and Schizophrenia (K-SADS) with parents and children. At the age of 9 years, mothers, fathers and youth completed the Child Depression Inventory (CDI) and the Screen for Child Anxiety Related Disorders, and teachers and K-SADS interviewers completed measures of peer functioning. Significant demographic covariates were included in all models. RESULTS: DMDD at the age of 6 years predicted a current diagnosis of DMDD at the age of 9 years. DMDD at the age of 6 years also predicted current and lifetime depressive disorder and attention-deficit/hyperactivity disorder (ADHD) at the age of 9 years, after controlling for all age 6 years psychiatric disorders. In addition, DMDD predicted depressive, ADHD and disruptive behavior disorder symptoms on the K-SADS, and maternal and paternal reports of depressive symptoms on the CDI, after controlling for the corresponding symptom scale at the age of 6 years. Last, DMDD at the age of 6 years predicted greater functional impairment, peer problems and educational support service use at the age of 9 years, after controlling for all psychiatric disorders at the age of 6 years. CONCLUSIONS: Children with DMDD are at high risk for impaired functioning across childhood, and this risk is not accounted for by co-morbid conditions.

The impact of etiology in lesion-symptom mapping - A direct comparison between tumor and stroke.

INTRODUCTION: Lesion-symptom mapping is a key tool in understanding the relationship between brain structures and behavior. However, the behavioral consequences of lesions from different etiologies may vary because of how they affect brain tissue and how they are distributed. The inclusion of different etiologies would increase the statistical power but has been critically debated. Meanwhile, findings from lesion studies are a valuable resource for clinicians and used across different etiologies. Therefore, the main objective of the present study was to directly compare lesion-symptom maps for memory and language functions from two populations, a tumor versus a stroke population. METHODS: Data from two different studies were combined. Both the brain tumor (N = 196) and stroke (N = 147) patient populations underwent neuropsychological testing and an MRI, pre-operatively for the tumor population and within three months after stroke. For this study, we selected two internationally widely used standardized cognitive tasks, the Rey Auditory Verbal Learning Test and the Verbal Fluency Test. We used a state-of-the-art machine learning-based, multivariate voxel-wise approach to produce lesion-symptom maps for these cognitive tasks for both populations separately and combined. RESULTS: Our lesion-symptom mapping results for the separate patient populations largely followed the expected neuroanatomical pattern based on previous literature. Substantial differences in lesion distribution hindered direct comparison. Still, in brain areas with adequate coverage in both groups, considerable LSM differences between the two populations were present for both memory and fluency tasks. Post-hoc analyses of these locations confirmed that the cognitive consequences of focal brain damage varied between etiologies. CONCLUSION: The differences in the lesion-symptom maps between the stroke and tumor population could partly be explained by differences in lesion volume and topography. Despite these methodological limitations, both the lesion-symptom mapping results and the post-hoc analyses confirmed that etiology matters when investigating the cognitive consequences of lesions with lesion-symptom mapping. Therefore, caution is advised with generalizing lesion-symptom results across etiologies.

Tocolytic effectiveness of nifedipine versus ritodrine and follow-up of newborns: a randomised controlled trial.

BACKGROUND: Several studies have demonstrated the superior tocolytic effectiveness of nifedipine over ritodrine. Only 1 trial conducted a long-term follow-up of newborns and found no difference in psychosocial and motor functioning. In a randomised, multicentre trial, we compared the tocolytic effectiveness of nifedipine and ritodrine and included a long-term follow-up of the newborns after 2 years of age. METHODS: Patients with imminent preterm labour were randomised and received either nifedipine or ritodrine. Side-effects, tocolytic effectiveness and neonatal outcome were studied. Development of the children was studied after the age of 2 years by a parental questionnaire. RESULTS: Ninety-three patients were included. Birth was postponed for an average of 4.3 weeks in the ritodrine group and 5.0 weeks in the nifedipine group (p=0.4). Patients who received ritodrine experienced significantly more side-effects compared to patients who received nifedipine (29 versus 4%, p<0.05). No significant differences were found in either group for average birth weight, Apgar scores after 1 min, neonatal intensive care unit (NICU) admission and neonatal complications. Parental questionnaires after 2 years had a response rate of 70%. Two-thirds of the children had developed normally in both groups. In both groups, only a few children were severely retarded (n=4). No significant differences in development were found between the 2 groups. CONCLUSIONS: Both nifedipine and ritodrine proved effective tocolytic drugs, however ritodrine caused significantly more maternal side-effects. Neonatal outcome and long-term development after 2 years of age were not significantly different. We favour nifedipine over ritodrine as a tocolytic drug.

Transcatheter tubal sterilization in rabbits. Technique and results.

RATIONALE AND OBJECTIVES: A potential method of nonsurgical tubal sterilization was tested in rabbits. METHODS: Metal coils were designed which could be placed into the uterotubal junction using transvaginal fluoroscopic fallopian tube catheterization. These metal coils were successfully placed unilaterally in the uterotubal junction of 32 rabbits. The contralateral fallopian tube and uterus were used as a control. The rabbits were bred, and the presence of pregnancies was confirmed by palpation. RESULTS: In 21 rabbits (66%), the coil stayed in place. Sixteen rabbits had multiple gestations on the side without the coil and no gestations on the side with the coil. Three rabbits had gestations on both sides, even though the coil was in place, and two rabbits never conceived. In 11 rabbits (34%) the coil was dislodged as early as 5 days and as late as 18 weeks after the procedure. Five of these 11 rabbits had bilateral embryos, 4 had embryos only on the side contralateral to where the coil had been, and 2 never conceived. CONCLUSIONS: The metal coil does prevent conception if it stays in place at the uterotubal junction. However, the coil failed to prevent pregnancy in 3 of 19 rabbits, and was dislodged in 11 rabbits, giving an overall failure rate for contraception of 44%.

Characterisation of aerobic gram-negative bacteria from subgingival sites of dogs--potential bite wound pathogens.

Ninety-eight aerobic, gram-negative bacterial isolates from subgingival samples from family-owned dogs with naturally occurring periodontitis were characterised phenotypically by conventional biochemical testing, by cellular fatty acid profiling and by the use of commercial identification systems. The majority (48, 81%) of the fermentative isolates but only 18% of the non-fermenters were identified by conventional biochemical testing alone. With additional cellular fatty acid profiling, another 7 (12%) fermentative and 23 (59%) non-fermentative isolates were identified to genus or group level. Cellular fatty acid analysis was essential for the identification of most non-fermenters, many of which are difficult to identify due to a paucity of positive reactions in routine biochemical tests. Commercial identification systems were less useful and did not contribute to further identification of these problematic isolates. This study underlines the difficulties encountered in the identification of canine oral bacteria--a group of potential bite wound pathogens--and presents schemes for microbiology laboratories to characterise such isolates.

Pelvic inflammatory disease with intrauterine device use: a reassessment.

This reassessment of IUDs as a risk factor for PID contrasts study results from prospective and case-control studies. Except for a transient increased risk after IUD insertions, increased risk is seen mainly in case-control studies after 1973, the time of a major PID epidemic and adverse publicity related to the Dalkon Shield. Removal of oral contraceptive users from case-control studies generally reduces their reported odds ratios, frequently to borderline statistical significance for studies with high accuracy of PID diagnosis. The remaining elevated odds ratios likely relate to diagnostic bias as primary care clinicians are more likely to refer patients wearing an IUD to referral centers where case-control studies are conducted. Biased case-control studies provided evidence for expensive litigation, resulting in removal of IUDs from the American market. The Food and Drug Administration requirements for postmarketing surveillance are inadequate to provide prospective data to avoid this kind of loss.

PIP: A reassessment of the relation between IUD use and pelvic inflammatory disease (PID) suggests that the correlation may not be supported by prospective cohort studies. The increased risk of pelvic inflammatory disease associated with IUD use was based primarily on case control studies after 1973, at which time there was a major PID epidemic and adverse publicity about the Dalkon Shield. Because case control studies may have been biased, these studies should not form the basis for the current consensus that IUD use increases the risk of PID. Problems with case-control studies include inaccuracy of PID diagnosis, the removal of oral contraceptive users from such studies, and miscalculations about the relative risk of PID. Another important factor is the increased incidence of sexually transmitted disease. These factors contributed to the current teaching in medical schools that IUD use increases the risk of PID. Although there is a small increased risk of PID in IUD users, due primarily to contamination of the uterine cavity during insertion, the risk is low. A comparison of case-control studies with prospective cohort studies does not support the association between IUD use and PID, and this should be considered when recommendations are made to physicians from developing countries. The potential of such instruction in influencing family planning policy decisions could have serious consequences for developing countries.

Was the Dalkon Shield a safe and effective intrauterine device? The conflict between case-control and clinical trial study findings.

OBJECTIVE: To compare the findings of the case-control and cohort studies used to indict the Dalkon Shield (A.H. Robins Company, Inc., Richmond, VA) with the findings of the Dalkon Shield clinical trials. DATA IDENTIFICATION: All published reports on the Dalkon Shield were identified through MEDLARS system (United States National Library of Medicine) searches and by cross checking all references in these reports. The same approach was used to identify all case-control and cohort studies of the purported relationship between intrauterine devices (IUDs) and pelvic inflammatory disease (PID). STUDY SELECTION: Only studies of interval patients that included 50 or more women and 6 or more months of follow up that computed standard IUD event rates (rates of pregnancy and expulsion and removal for pain and bleeding) were selected for this study. All case-control and cohort studies identified were included except two case-control studies that included women with sterile chronic salpingitis. RESULTS: The 16 case-control and 2 cohort studies found or suggested that the Dalkon Shield increased the risk of PID. The 71 clinical trials of the Dalkon Shield show that when this device is inserted by an experienced clinician it is a safe and effective contraceptive method, comparable with other IUDs used at the time. There was no evidence of an increased risk of PID found in these clinical trials. CONCLUSIONS: This study offers convincing evidence that the indictment of the Dalkon Shield was a mistake. Additionally, this study shows that physician skill and experience is far more important to successful IUD insertion than previously recognized, a finding with considerable implications for IUD study designs and for marketing strategies.

PIP: 2 researchers searched MEDLARS databases for articles on clinical trials of the Dalkon Shield to compare the results of case control and cohort studies which identified its relationship with pelvic inflammatory disease (PID) with those of other clinical trials. They identified 71 useful reports. The results of clinical trials not used to incriminate the A.H. Robins Company, the manufacturer of the Dalkon Shield, showed that the Dalkon Shield was indeed safe and effective when inserted by a skilled and experienced clinician. In addition, the Dalkon Shield compared favorably with other IUDs. Further the pregnancy rate and removal rate for pain and bleeding matched those of other IUDs. Moreover the expulsion rate for the Dalkon Shield was better than that of other IUDs. In those studies that examined PID, the PID rates were essentially the same as the expected rates of other IUDs in their clinic populations. Besides, even though the case control studies suggested a considerable increased PID rates with the Dalkon Shield, increased rates of removals for pain and bleeding did not occur. Furthermore pregnancy and expulsion rates improved as did the skill and experience of the physicians who inserted the Dalkon Shield. In fact, the best rates occurred in trials conducted in centers where only a few clinicians inserted 1000 Dalkon Shields. For example, the removal rate for pain or bleeding was as low as 0.9%. This rate among inexperienced clinicians was as high as 27%. The fact that the litigation case against A.H. Robins used the results of the weaker case control studies rather than the superior randomized clinical trial resulted in removal of a safe and effective contraceptive. Further IUD studies should incorporate clinician skill as a variable to better assess the IUD's efficacy and safety.

Potential demand for voluntary female sterilization in the 1980s: the compelling need for a nonsurgical method.

PIP: The authors estimate the potential world demand for voluntary sterilization on the basis of U.S. data which shows that 31.3% of U.S. married women of reproductive age are sterilized. If sterilization were equally available elsewhere, they estimate that approximately 180 million procedures would be required during the 1980s, or a five-fold increase over the number now being performed. Of presently available methods colpotomy, culdoscopy, the tantalum clip, and hysteroscopy are not satisfactory. In the author's view, minilaparotomy is the safest procedure, especially when performed by less specialized junior physicians and in rural areas. The most promising new methods use chemicals instilled into the fallopian tubes. Quinacrine pellets inserted through an IUD inserter have an estimated lifetime failure rate of 3/100 women. The authors consider this a safe approach costing about 1/2 as much as surgical sterilization. The quinacrine method has the potential to meet estimated developing country needs and also to be widely used in developed countries. They urge priority for further research on this method.^ieng

Menstrual regulation in the United States: a preliminary report.

The efficacy and safety of vacuum aspiration on an outpatient basis without anesthesia or cervical dilatation within 14 days of a missed menstrual period was evaluated in 1,009 women. Among those patients in whom pregnancy could be documented (54.8%), 4.2% were still pregnant after the procedure. Potentially serious complications were pelvic infection (0.4%), bleeding requiring a repeat curettage (0.3%), and prolonged bleeding (0.7%). For comfort, 26.7% received local anesthesia or analgesia. To allow selection of a higher proportion of pregnant patients, the probability of pregnancy was derived for patients with either a positive or negative pregnancy test at each length of amenorrhea. To determine the best vacuum pressure and source, and the cannula size and type at each duration of pregnancy, a more extensive (large, controlled, comparative) study is required.

Two modifications of the intrauterine membrane contraceptive device.

The intrauterine membrane (IUM) is an intrauterine contraceptive device designed to be compliant with a range of uterine shapes and sizes and with transient dimensional changes resulting from uterine motility. This compliance was expected to contribute to low rates for removal due to bleeding and pain, but the use of the IUM resulted in heavy bleeding among its early users. Consequently, two modifications of the device were made to decrease bleeding. One group of IUMs was modified by using ethylene vinyl acetate to provide a high level of lateral compliance and another was modified by using a tissue-compatible Hydron coating in order to decrease the inflammatory response of the endometrium. One hundred of each of these modified IUMs were tested along with 100 of the standard IUMs in a double-blind study conducted at the Noi Klinika in Debrecen, Hungary. The findings of this study suggested that these two modifications did not improve the over-all performance of the IUM.

Efficacy and safety of repeated transcervical quinacrine pellet insertions for female sterilization.

OBJECTIVE: To investigate the rates of tubal occlusion, pregnancy, and side effects of repeated, monthly transcervical insertions of 252 mg quinacrine as pellets. DESIGN: Clinical trial among 159 reproductive age women receiving two monthly transcervical insertions of 252 mg of quinacrine followed by hysterosalpingograms (HSGs) 1 month after last insertion and an additional monthly insertion among women without evidence of bilateral tubal occlusion. Contraception of women's choice provided until bilateral tubal occlusion achieved, and surgical sterilization provided for women failing to achieve bilateral tubal occlusion after third quinacrine insertion. Women were followed for at least 24 months for evidence of pregnancy or side effects. RESULTS: Among the 159 women completing the protocol, 73% had evidence of bilateral tubal occlusion by HSGs after two insertions of quinacrine pellets and 94% after a third insertion. These 149 women were followed for 24 months without a pregnancy failure or serious side effect. CONCLUSION: Transcervical applications of quinacrine as pellets have potential for safe, effective, inexpensive, and easily deliverable female sterilization.

PIP: Between January 1988 and April 1988, physicians inserted at least 2 252 mg quinacrine pellets into the uterus via the cervix (1 month apart during days 5 to 18 of consecutive menstrual cycles) in 159 34-to-39-year-old women at the outpatient clinic at Boulak El-Dakrour Hospital in Giza, Egypt. 1 month after each insertion, they used hysterosalpingograms to determine tubal patency. They inserted a 3rd pellet if at least 1 tube remained patent. The women used additional contraceptives from first insertion to 1 month after the last insertion to prevent unwanted pregnancy. The physicians followed the women for 24 months. Quinacrine-induced menstrual changes, e.g., intermenstrual bleeding (13.2%) and amenorrhea (26.4%), basically disappeared by 6 months. Quinacrine abated heavy or prolonged menses in women who suffered from it beforehand. 84.3% did not experience any complications or had no complaints related to quinacrine insertion. Occlusion occurred in both tubes after 2 insertions in 73% of cases and after 3 insertions in 93.7%. Women who did not have any bleeding experienced tubal occlusion more readily than those who did (after 2 insertions, 80.8% vs. 69.2%). In fact, absence of blood in the uterus resulted in 100% efficacy after 3 insertions compared to only 90.7% in those who did bleed (p = .02). After 3 insertions, women whose uterus was longer than 8 cm were less likely to have occluded tubes than those whose uterus was at the most 8 cm long (87.2% vs. 95.8%; p = .09). In fact, they had the lowest tubal occlusion rate. None of the women with 2 occluded tubes at 24 months became pregnant. They did not use any contraception beginning 1 month after last insertion. These results indicate that quinacrine pellets are an effective and safe method of nonsurgical sterilization.

A randomized controlled study comparing the endocrine effects of pulsatile intravenous gonadotropin-releasing hormone after gonadotropin-releasing hormone agonist pretreatment versus clomiphene citrate in patients with polycystic ovary syndrome.

OBJECTIVE: To compare the endocrine changes in the follicular phase in infertile patients with polycystic ovary syndrome (PCOS) treated with either pulsatile IV GnRH after GnRH-agonist (GnRH-a) down-regulation or clomiphene citrate (CC). DESIGN: Subgroup analysis within a randomized, controlled, multicenter study. SETTING: Women referred to the Infertility Clinic, Catharina Hospital Eindhoven, The Netherlands. PATIENT(S): Twenty-eight infertile patients with PCOS. INTERVENTIONs): Patients were randomly assigned to pulsatile IV GnRH (10-20 microgram/90 min) after GnRH-a down-regulation or CC (50-150 mg; cycle days 3-7). Patients were monitored on alternate days with ovarian sonography and serum concentrations of E(2), LH, and FSH. Serum P and sonography confirmed ovulation. MAIN OUTCOME MEASURE(S): Serum concentrations of E(2), LH, and FSH were assessed before treatment was started and after each ovarian sonography. RESULT(S): In ovulatory cycles, no statistically significant differences were observed during the follicular phase comparing serum concentrations of E(2), LH, and FSH between the treatments. However, a significant increase in LH occurred in the GnRH group. CONCLUSION(S): No significant endocrine differences were observed between GnRH and CC treatment. However, there was a significant increase in the serum LH concentration during the follicular phase in the GnRH group. Increments of LH in the GnRH group may be due to recovery of endogenous LH secretion.

Toward stationary populations and beyond.

The world's rate of population growth is declining. Most industrialized societies have achieved or are moving rapidly toward stationary populations, but while birth rates are also declining in many developing countries, continued growth must be expected because of the large proportions of young people in these populations. New evidence of exceptions to the classical demographic transition theory indicate that declining fertility is compatible with high mortality or low socioeconomic development if acceptable means of fertility control are readily available. "Fertility silhouettes" showing differing age-specific fertility rates indicate that present family planning programs have had a demographic impact. A review of the economic and ecologic consequences of rapid population growth justifies the conclusion that considerable effort will be required to again bring the world's population into balance with these systems. The author outlines priorities for this effort, with emphasis on the need to devise acceptable means of fertility control that will not tax the frail health care infrastructures of developing countries.

Quinacrine sterilization: a retrospective.

OBJECTIVE: To trace development of quinacrine sterilization (QS). METHODS: Review of published reports. RESULTS: The high prevalence of septic abortion among high parity women in Santiago, Chile, motivated Zipper to find a safe, inexpensive method of non-surgical female sterilization. Various cytotoxic drugs were tried in rats. Because quinacrine was already accepted for intrapleural injection it was chosen for the first clinical trial. A slurry consisting of quinacrine and xylocaine was instilled into the uterine cavity with a transcervical syringe. Reasonable efficacy was noted and a limited scar of the intramural tube demonstrated. However, a side effect of cortical excitation and reports of 3 deaths ended this approach. Zipper and Wheeler hypothesized that the difficulty was due to rapid absorption of quinacrine under pressure and designed a pellet form that dissolves slowly and could be delivered transcervically using a modified IUD inserter. A standard protocol of 252 mg in seven 36 mg pellets placed at the uterine fundus on two occasions a month apart has now been widely used with considerable evidence for safety and efficacy. Indeed, protection is greater than 98% at 2 years of use. CONCLUSION: QS is ready for widespread use, especially where surgical sterilization is not safely available or when women are poor candidates for surgery or have such a fear of surgery that they will not seek surgical sterilization.

Follow-up study of oral contraceptive acceptors in Howrah District in India.

In the Howrah District in India, three clinics--one in each of the urban, slum, and rural areas of the city--were initiated by the Humanity Association of Howrah in November of 1968 to supply oral contraceptives (OCs) to women from 15 to 45 years of age. The project was discontinued in September, 1972. Of the 1700 patients still active when the project ended, 1527 were contacted for the follow-up survey. Findings indicate that most women in this district were satisfied with OCs and would continue to use them if they were available. In corroboration of this, it was found that 43% of the women had used OC'S obtained from other sources after the project was discontinued. While 35.5% of the women who used no contraceptive method after project ended reported becoming pregnant or suspected that they were pregnant at the time of the interview, only 4.2% of those who reported using some form of contraception reported pregnancy or suspected pregnancy. The demographic impact of the project will be evaluated on the basis of data to be obtained in a subsequent survey of the same communities.

Immediate postpartum insertion of a sutured Lippes Loop.

Use of the sutured Lippes Loop for immediate postpartum insertion was evaluated in 100 volunteers at the Kasr-el-Aini Hospital in Cairo. The intrauterine devices were inserted manually immediately after delivery of the placenta. There was an expulsion rate of 1.2 per 100 women at three months, one case of infection requiring treatment and one removal because of bleeding. One woman became pregnant and expelled the Loop. The two major problems associated with the use of an intrauterine device, high expulsion rate and perforation, were overcome by hand insertion of the Loop.

Estrogen-progesterone withdrawal bleeding in diagnosis of early pregnancy.

This study was designed to evaluate the efficacy of an exogenous estrogen-progesterone preparation for inducing "withdrawal bleeding" in non-pregnant women, a procedure used in some areas for the diagnosis of early pregnancy. Three hundred patients not desiring to be pregnant and with no signs of pregnancy other than menses delayed by 14 days or less were randomly assigned to treatment or control groups. The treatment group received an intramuscular injection of 50 mg progesterone and 3 mg oestradiol benzoate in oil. The control group received no hormonal injection. There was no significant difference between the two groups in the incidence of uterine bleeding within 7 days. Thus, the hormonal preparation was ineffective in inducing "withdrawal bleeding". Its use as a diagnostic test for pregnancy is not recommended.

International maternity care monitoring: results of a pretest.

This report gives the preliminary results of a pretest cosponsored by the International Fertility Research Program and the International Federation of Gynaecology and Obstetrics. It includes data on 33 116 deliveries in 20 maternity centers in Latin America, Europe, Africa and Asia. The findings are organized around four themes: (a) family formation and reproductive history, (b) family health, (c) management of this delivery and (d) desired family size and family planning practices.