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The efficacy of trauma-focused treatments for children and adolescents is well researched. However, less is known about the long-term and caregiver-reported effects. Searched databases were PsychInfo, MEDLINE, Cochrane Library, PTSDPubs, PubMed, Web of Science, and OpenGrey. Treatment effects of trauma-focused cognitive behavioral therapy (TF-CBT) were computed at 12-month follow-up with posttraumatic stress symptoms (PTSS) as primary outcome and symptoms of depression, anxiety, and grief as secondary outcomes. Concordance between participant and caregiver ratings were investigated. TF-CBT showed large improvements across all outcomes from pre-treatment to 12-month follow-up (PTSS: g = 1.71, CI 1.27-2.15) and favorable results compared to active treatments and treatment as usual at 12-month follow-up (PTSS: g = .35, CI .13-.56). More pronounced effects were found in group settings. No significant differences were detected between participant and caregiver ratings with high reliability across almost all outcomes and assessment points. TF-CBT is a reliable treatment for pediatric PTSS and secondary symptoms with stable results at 12-month follow-up.

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OBJECTIVE: The aim of this study was to investigate long-term post-recurrence survival outcomes in young women receiving fertility-sparing surgery (FSS) to verify the feasibility of the limited surgery for epithelial ovarian cancer (OvCa). STUDY DESIGN: We performed a regional multicenter retrospective study from January 1986 and March 2020, using clinical data corrected under the central pathological review system. Patients with recurrent tumor after surgery for stage I epithelial OvCa, aged equal or younger than 45 years were included for this study. We evaluated effect of FSS regarding long-term post-recurrence survival with statistical adjustment of propensity score-based method. RESULTS: With the Kaplan-Meier method, original and adjusted survival curves were estimated for recurrence-after survival of patients with (n = 14) and without FSS (n = 26). Median time to disease-specific death was 18.6 months. In both original and adjusted cohorts, there were no significant difference between the two groups (log rank test; P > 0.05). Hazard ratio of disease-specific death was 1.264 (95% confidence interval, 0.563-2.836; P = 0.570) in original and 1.354 (95% confidence interval, 0.702-2.611; P = 0.366) in adjusted population. This result indicated that patients with FSS was not associated with poorer prognosis for recurrence-after survival than those without. When comparing patients not receiving FSS, patients receiving FSS with recurrence at spared ovary followed not significantly different survival outcome as well as those with extra-ovarian recurrence. CONCLUSION: There was no significant difference of long-term post-recurrence survival outcomes between patients of epithelial OvCa with and without FSS in young women of reproductive age.

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INTRODUCTION: Studies have shown that long-term positive behavioural and physiological changes are induced in connection with vaginal, physiological birth, and skin-to-skin contact after birth in mothers and babies. Some of these effects are consistent with the effect profile of oxytocin. This scoping review explores whether epigenetic changes of the oxytocin gene and of the oxytocin receptor gene (OTR) are involved in these effects. METHODS: We searched Pubmed, Medline, BioMed Central, Cochrane Library, OVID, and Web of Science for evidence of epigenetic changes in connection with childbirth in humans, with a particular focus on the oxytocin system. RESULTS: There were no published studies identified that were related to epigenetic changes of oxytocin and its receptor in connection with labour, birth, and skin-to-skin contact after birth in mothers and babies. However, some studies were identified that showed polymorphisms of the oxytocin receptor influenced the progress of labour. We also identified studies in which the level of global methylation was measured in vaginal birth and caesarean section, with conflicting results. Some studies identified differences in the level of methylation of single genes linked to various effects, for example, immune response, metabolism, and inflammation. In some of these cases, the level of methylation was associated with the duration of labour or mode of birth. We also identified some studies that demonstrated long-term effects of mode of birth and of skin-to-skin contact linked to changes in oxytocin function. CONCLUSION: There were no studies identified that showed epigenetic changes of the oxytocin system in connection with physiological birth. The lack of evidence, so far, regarding epigenetic changes did not exclude future demonstrations of such effects, as there was a definite role of oxytocin in creating long-term effects during the perinatal period. Such studies may not have been performed. Alternatively, the oxytocin linked effects might be indirectly mediated via other receptors and signalling systems. We conclude that there is a significant lack of research examining long-term changes of oxytocin function and long-term oxytocin mediated adaptive effects induced during physiological birth and skin-to-skin contact after birth in mothers and their infants.

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Introduction: Adults Born Very Preterm (ABP) are an underperceived but steadily increasing patient population. It has been shown that they face multiple physical, mental and emotional health problems as they age. Very little is known about their specific health care needs beyond childhood and adolescence. This article focuses on their personal perspectives: it explores how they feel embedded in established health care structures and points to health care-related barriers they face. Methods: We conducted 20 individual in-depth interviews with adults born preterm aged 20-54 years with a gestational age (GA) below 33 weeks at birth and birth weights ranging from 870-1,950 g. Qualitative content analysis of the narrative interview data was conducted to identify themes related to self-perceived health, health care satisfaction, and social well-being. Results: The majority (85%) of the study participants reported that their former prematurity is still of concern in their everyday lives as adults. The prevalence of self-reported physical (65%) and mental (45%) long-term sequelae of prematurity was high. Most participants expressed dissatisfaction with health care services regarding their former prematurity. Lack of consideration for their prematurity status by adult health care providers and the invisibility of the often subtle impairments they face were named as main barriers to receiving adequate health care. Age and burden of disease were important factors influencing participants' perception of their own health and their health care satisfaction. All participants expressed great interest in the provision of specialized, custom-tailored health-care services, taking the individual history of prematurity into account. Discussion: Adults born preterm are a patient population underperceived by the health care system. Longterm effects of very preterm birth, affecting various domains of life, may become a substantial burden of disease in a subgroup of formerly preterm individuals and should therefore be taken into consideration by adult health care providers.

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OBJECTIVE: To determine the influence of depot medroxyprogesterone acetate (MPA) on bone mineral density when used as a contraceptive method. DESIGN: Cross-sectional study. SETTING: Academic tertiary-care hospital. PATIENT(S): Fifty premenopausal women who had used depot MPA as a contraceptive method for > or =1 year and 50 women who had never used hormonal contraceptive methods. INTERVENTION(S): Bone mineral density was evaluated at the midshaft and at the distal radius of the nondominant forearm using single x-ray absorptiometry. MAIN OUTCOME MEASURE(S): Bone mineral density. RESULT(S): Bone mineral density at the midshaft of the forearm was lower in depot MPA users than in women who had never used hormonal contraceptive methods, but the difference was not statistically significant. At the distal portion, bone mineral density was significantly lower in the study group. The duration of depot MPA use was not related to bone mineral density. CONCLUSION(S): Women > or =35 years of age presented with a lower bone mineral density only at the distal portion of the forearm after the use of depot MPA for > or =1 year. However, this decrease was not related to the duration of depot MPA use. It is not possible to conclude that women who use depot MPA are at risk of osteoporosis.

PIP: The impact of depot medroxyprogesterone acetate use on bone mineral density was assessed in a cross-sectional study of 100 women recruited from a teaching hospital in Campinas, Brazil, during 1996-98. Bone mineral density, as evaluated at the midshaft and distal radius of the nondominant forearm by single x-ray absorptiometry, was compared in 50 women 35-45 years of age who had been using Depo-Provera for contraception for 1 year or more (mean duration, 46.4 +or- 38.6 months) but had never used any other hormonal method and 50 age- and weight-matched women who had never used any form of hormonal contraception. Although mean bone mineral density at the midshaft of the forearm was lower in Depo-Provera users than nonusers of hormonal contraception (0.459 +or- 0.042 vs. 0.474 +or- 0.049 g/sq. cm), the difference was not statistically significant. At the distal portion, bone mineral density was significantly lower in Depo-Provera users than nonusers of hormonal methods (0.362 +or- 0.040 vs. 0.392 +or- 0.049 g/sq. cm, p 0.001). The duration of Depo-Provera use was not related to bone mineral density, even when women had used the method for more than 5 years. Multiple regression analysis indicated that 4 pregnancies, White race, and Depo-Provera use were significantly associated with lower bone mineral density at the midshaft section of the forearm; at the distal section of the forearm, these variables were Depo-Provera use, more than 4 pregnancies, White race, older age at menarche, and habitual coffee drinking. These findings do not provide sufficient evidence to conclude that Depo-Provera users are at increased risk of osteoporosis.

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The association between long-term use of depot-medroxyprogesterone acetate (DMPA) and bone mineral density (BMD) has been controversial, as seen in three case-control studies in New Zealand, Thailand, and the United Kingdom. In the present case-controlled study of BMD, a group of 67 Chinese women who had used DMPA from 5-15 years was compared with 218 women of the same age range who had not used any steroidal hormones. DMPA users were found to have a significantly lower BMD at lumbar vertebra (L2-4) (0.93 g/cm2), neck of femur (0.69 g/cm2), trochanter (0.59 g/cm2), and Ward's triangle (0.58 g/cm2), as compared with the control group, whose corresponding BMD values were 1.03 g/cm2, 0.83 g/cm2, 0.71 g/cm2, and 0.78 g/cm2, respectively (p < 0.001). The average percentage of bone loss per year was estimated to be 1.1% in L2-4, 2.3% in neck of femur, 2.4% in trochanter, and 3.5% in Ward's triangle. The percentage of bone loss in L2-4 was found to be more pronounced with age. This study provided information that the use of DMPA in a Chinese group for > 5 years in associated with bone loss, and a prospective study is needed to confirm these data, which are different from two case-control studies.

PIP: The effect of long-term use of depot medroxyprogesterone acetate (DMPA) on bone mineral density remains controversial. The present study compared bone mineral densities in 67 long-term (5 years or more) DMPA users recruited consecutively from the Hong Kong (China) Family Planning Association with those in 218 age-matched controls recruited from 8 family health service clinics in Hong Kong. Mean age was 42.8 years (range, 34-46 years) in the DMPA group and 40.0 years (range, 34-46 years) among controls. Body mass index, calcium intake, and smoking were similar in both groups. The median duration of DMPA use was 6 years (range, 5-15 years). Long-term DMPA users had significantly lower bone mineral densities than controls at the lumbar vertebra (0.93 vs. 1.03 g/sq. cm), neck of femur (0.69 vs. 0.83 g/sq. cm), trochanter (0.59 vs. 0.71 g/sq. cm), and Ward's triangle (0.58 vs. 0.78 g/sq. cm). The percentage of bone loss in L2-4 was more pronounced with increasing age. For each year of DMPA use, the decrease in bone mineral density was estimated to be 0.011 g/sq. cm (1.1%) in L2-4, 0.0193 g/sq. cm (2.3%) in the neck of femur, 0.0169 g/sq. cm (2.4%) in the trochanter, and 0.0277 g/sq. cm (3.5%) in Ward's triangle.

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Little is known about the long-term impact of reproductive experiences on women's lives. This paper uses questionnaire data collected from 107 White female college graduates, when they were approximately 47 years old. More than half the sample had experienced at least one type of reproductive difficulty (abortion, miscarriage, or infertility). The stress and coping model of life difficulties (Lazarus and Folkman, 1984) was used to examine the relationship between the women's reproductive difficulties and emotional sequelae, politicization, and orientation to motherhood at midlife. As predicted, emotional responses to the reproductive difficulties varied according to the particular nature of each experience. In addition, women who had abortions and no other difficulties were more politicized at midlife than other women. Women whose reproductive experiences were especially likely to arouse feelings of not being in control of their life (those who had miscarriages or infertility) described a more agentic orientation to motherhood when compared with other women.

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Many studies have shown that oral contraceptive (OC) use increases a young woman's risk of breast cancer, although some studies suggest that the risk may be limited to recent use. The objective of this study was to determine what particular aspects of OC use could be important for breast cancer development at an early age in the cohort of women who had the opportunity to use OCs all of their reproductive life. The cases were first diagnosed with breast cancer at age 40 or younger between 1983 and 1988, and identified by the Los Angeles County Cancer Surveillance Program. Control subjects were individually matched to participating cases on birth date (within 36 months), race (white), parity (nulliparous versus parous), and neighborhood of residence. Detailed OC histories were obtained during in-person interviews with subjects. In general the risk estimates were small, and not statistically significant. Compared to no use, having used OCs for 12 years or more was associated with a modest non-significant elevated breast cancer risk with an odds ratio (OR) of 1.4 (95% confidence interval (CI) = 0.8-2.4). Long-term (12 years or more) users of high-dose estrogen pills had a non-significant 60% higher breast cancer risk than never users (CI = 0.9-3.2). Early use was associated with slightly higher ORs among young women (age < or =35), and among parous women. Recent use was associated with somewhat higher ORs among parous women and women above age 36. Analyses by stage, body weight, and family history yielded similar results. This study is consistent with a modest effect of early OC use on breast cancer risk in young women.

PIP: The relationship of breast cancer risk in young women to particular patterns of oral contraceptive (OC) use was investigated in a case-control study conducted in Los Angeles County, California (US), in 1983-89. Enrolled as cases were 744 White women 40 years or younger at the time of breast cancer diagnosis who were located through a population-based cancer registry. One community control was matched to each of these cases on birth date, race, parity, and neighborhood of residence. OCs had been used by 83.3% of breast cancer cases and 84.4% of controls; 68.6% of cases and 69.3% of controls had used OCs for 12 months or more. In general, the results revealed only a modest effect of early OC use on breast cancer risk in young women. Compared to never use, OC use for 12 or more years was associated with a small, nonsignificant elevated breast cancer risk (odds ratio (OR), 1.40; 95% confidence interval (CI), 0.81-2.40). Women who used high-dose estrogen formulations for 12 years or more had a nonsignificant increased risk compared with nonusers (OR, 1.64; 95% CI, 0.85-3.18). Among women below age 35 years at diagnosis, compared with never users, women who had used OCs for 1 year or more before the age of 18 years were at almost twice the risk of developing breast cancer (OR, 1.97; 95% CI, 0.90-4.32). Among women over age 35 years at diagnosis, compared with never users, those who had used OCs for 3 or more years during the past 5 years were at a 2.54-fold increased risk (95% CI, 0.94-6.88). Analyses by cancer stage, body weight, and family history failed to detect any significant effects.

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This article describes the long-term consequences of successful cardiovascular disease (CVD) prevention and its influence on premature mortality in Finland, with special reference to North Karelia. Active community-based CVD prevention began in 1972 in the province of North Karelia (population, 180,000). Since 1977, active preventive work has been carried out nationwide, taking advantage of the experience from North Karelia, which continued as a demonstration area for integrated prevention of noncommunicable diseases. Comprehensive community-based interventions as part of WHO interhealth and CINDI programmes in North Karelia and nationwide aimed at changing the target risk factors and health behaviours (serum cholesterol, blood pressure, smoking, diet) at the population level. Age-adjusted mortality rates for CVD, coronary heart disease (CHD), cerebrovascular disease, all cancers, lung cancer, accidents and violence, and all causes in the population aged 35-64 years from the pre-programme period (1969-71) to 1995 were the main measures of the outcome. Among men there was a great reduction in deaths from CHD, CVD, cancer, and all causes in the whole country. From 1969-71 to 1995 the age-standardized CHD mortality (per 100,000) decreased in North Karelia by 73% (from 672 to 185) and nationwide by 65% (from 465 to 165). The reduction in CVD mortality was of the same magnitude. Among men, CHD mortality decreased in the 1970s, as did lung cancer mortality in the 1980s and 1990s, significantly more in North Karelia than in all of Finland. Among women there was a great reduction in CVD (including CHD and stroke) mortality and all-causes mortality, but only a small reduction in cancer mortality. These results show that a major reduction in CVD mortality among the working-age population can take place in association with active reduction of major risk factors, with a favourable impact on cancer and all-causes mortality.

PIP: "This article describes the long-term consequences of successful cardiovascular disease (CVD) prevention and its influence on premature mortality in Finland, with special reference to North Karelia.... Among men there was a great reduction in deaths from CHD [coronary heart disease], CVD, cancer, and all causes in the whole country. From 1969-71 to 1995 the age-standardized CHD mortality...decreased in North Karelia by 73%...and nationwide by 65%.... The reduction in CVD mortality was of the same magnitude. Among men, CHD mortality decreased in the 1970s, as did lung cancer mortality in the 1980s and 1990s, significantly more in North Karelia than in all of Finland. Among women there was a great reduction in CVD (including CHD and stroke) mortality and all-causes mortality, but only a small reduction in cancer mortality." (EXCERPT)

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The authors conducted a 2-year (1989-1991) community-based longitudinal study in a shantytown in Lima, Peru, to examine the effect of Cryptosporidium parvum infection on child growth during the year following the onset of infection. A cohort of children, aged 0-3 months at recruitment, was followed monthly for anthropometrics, weekly for stool samples, and daily for diarrheal status. Data from 185 children in the cohort permitted a comparison of growth in C. parvum-infected and noninfected children. The analyses fitted smooth, flexible curves with a linear random-effects model to estimate growth differences between C. parvum-infected and noninfected children. Children infected with C. parvum experienced growth faltering, both in weight and in height, for several months after the onset of infection, followed by a period of catch-up growth. Younger children took longer to catch up in weight than did older children. Catch-up growth, however, did not occur in children infected between ages 0 and 5 months. These children did not catch up in height, and one year after infection they exhibited an average deficit of 0.95 cm (95% confidence interval (CI) 0.38-1.53) relative to noninfected children of similar age. Stunted children who became infected also did not catch up in either weight or height, and one year after infection they exhibited a height deficit of 1.05 cm (95% CI 0.46-1.66) relative to noninfected, stunted children of similar age. These results indicate that Cryptosporidium parvum has a lasting adverse effect on linear (height) growth, especially when acquired during infancy and when children are stunted before they become infected.

PIP: A 2-year (1989-91) community-based study conducted in a shantytown in Lima, Peru, used regression splines to assess the effect of Cryptosporidium parvum infection on child growth during the year following the onset of infection. The 185 children 0-3 months of age at enrollment who comprised the study cohort underwent daily monitoring of diarrheal status, weekly stool analysis, and monthly anthropometric measurements. 88 children (48%) became infected with C. parvum during the study period. A linear random effects model was used to model differences in temporal growth patterns between C. parvum-infected and noninfected children. Children infected with C. parvum demonstrated growth faltering, both in weight and height, for several months after the onset of infection, followed by a period of catch-up growth. Younger age at infection intensified the effect of C. parvum infection on growth. In children infected between 0 and 5 months of age, catch-up weight gain was complete 6 months later but, 12 months after infection, these children exhibited an average height deficit of 0.95 cm relative to uninfected children the same age. Stunting also increased the magnitude and duration of the effect of C. parvum infection on growth. 12 months after infection onset, stunted children demonstrated a 1.05 cm height deficit relative to their noninfected, nonstunted age counterparts. These findings indicate that cryptosporidiosis has an adverse effect on child growth, especially when infection is acquired during infancy. C. parvum-related intestinal damage and malabsorption are presumed to be the mechanisms associated with growth retardation.

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OBJECTIVE: Our purpose was to determine the relationship between previous caesarean section and subsequent development of placenta praevia and placenta praevia with accreta. METHOD: A retrospective review of the case records of all women delivered with the diagnosis of placenta praevia during the 2-year period from January 1, 1995, to December 31, 1996, at the tertiary referral centre, Princess Badeea Teaching Hospital, in north Jordan. RESULTS: There were 18, 651 deliveries in the study period. 65 (0.35%) had placenta praevia, 21 (32.3%) of whom had a history of previous caesarean section. The incidence of placenta praevia was significantly increased in those with a previous caesarean section (1.87%) compared with those with an unscarred uterus (0.25%); p < 0.0001). This risk increased as the number of previous caesarean sections increased: 1.78% for one previous section; 2.4% for two, and 2.8% for three or more. The incidence of anterior placenta praevia and placenta accreta was significantly increased in those with previous caesarean scars. In the group without antecedent of caesarean section, accretism risk was 9%, with one section or more 40.8% (p < 0.005). CONCLUSION: There is a high association between anterior placenta praevia, placenta accreta and previous caesarean section. This was enhanced with the increasing number of previous caesarean sections. Patients with an antepartum diagnosis of placenta praevia who have had a previous caesarean section should be considered at high risk of developing placenta praevia and accreta.

PIP: The association between previous cesarean section delivery and subsequent development of placenta praevia and placenta praevia with accreta was investigated in a retrospective review of the records of all women delivered at Princess Badeea Teaching Hospital (Irbid, Jordan) in 1995-96 with a diagnosis of placenta praevia. The 65 women with placenta praevia represented 0.35% of total deliveries during the 2-year study period; 21 of these women (32.3%) had a history of previous cesarean section. The incidence of placenta praevia was significantly greater in women with a history of cesarean section than in those without such a history (1.87% and 0.25%, respectively; p 0.0001). This risk increased with increases in the number of previous surgical deliveries: 1.78% for 1, 2.4% for 2, and 2.8% for 3 or more. The incidence of placenta accreta also was significantly increased in women with previous cesarean section compared to those without a prior surgical delivery (40.8% and 9.0%, respectively; p 0.005).

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OBJECTIVE: To assess, using a computerised model, the effects on mortality of the use of combined oral contraceptives (COCs). DESIGN: Two hypothetical cohorts of one million women each, identical except for their use of contraception. The impact of COC use was explored by applying, to each cohort, death rates which were adjusted according to a series of assumptions about the risks associated with COC use. The model also explored the effects of a number of different patterns of COC use. SETTINGS AND SUBJECTS: Women aged 16, followed through to ages 50 and 75, exposed to 1994 UK death rates. MAIN OUTCOME MEASURES: Numbers of deaths from various cancers and cardiovascular diseases attributable to COC use. RESULTS: Based on the standard pattern of use, there were 1.7 per cent more deaths in the COC cohort to age 50. The important effects on mortality of different patterns of use and of different assumptions about risks in ex-users were illustrated. CONCLUSIONS: The results confirm the findings of earlier work and provide some reassurance about the likely adverse effects of COC use.

PIP: A computer model that takes account of state-of-the-art knowledge about the health risks and benefits of combined oral contraceptive (OC) use was applied to two hypothetical cohorts of 1 million women each aged 16 years and followed through to ages 50 and 75 years, exposed to 1994 UK death rates, who were identical except for contraceptive use. The effects of OC use were examined in relation to deaths from five cancers (ovarian, breast, cervical, endometrial, and liver), cardiovascular diseases (acute myocardial infarction, cerebral thrombosis, venous thromboembolism, and subarachnoid hemorrhage), and deaths associated with IUD use and sterilization. Among the five patterns of OC use included in the model, the standard was OC use from 16 to 29 years, IUD use from 30 to 39 years, and sterilization at age 40 years. Based on the standard pattern of use and standard risk assumptions, the number of deaths in the OC cohort at age 50 years was 1.7% higher than that in the control group, corresponding to an extra 465 deaths by age 50 years in a group of 1 million 16 year olds. To age 75 years, the number of deaths in the OC cohort was 0.5% lower than in the control group, corresponding to a benefit of 735 lives. The total number of deaths in the OC cohort compared to the control group ranged from an increase of 0.2-12.1% to age 50 years and from a decrease of 1.3% to an increase of 0.5% to age 75 years. Analysis of the standard set of assumptions against the standard pattern of use resulted in 22 fewer maternal deaths in the OC cohort than the control group. Although more research is needed on the implications of OC use well into the fifth decade of life, these results provide some reassurance about the likely adverse effects of OC use.

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OBJECTIVE: To identify any adverse effect on bone density in long term users of depot medroxyprogesterone acetate (DMPA) for contraception. DESIGN: Cross-sectional measurement of bone density in users with amenorrhoea of more than one year or any woman using DMPA for more than five years. SETTING: Community Family Planning Clinics in Portsmouth and Manchester. POPULATION: One hundred and eighty-five women aged 17-52 years (mean 33.3 years) who had used DMPA for between 1 and 16 years and were attending the clinics for further injections, between August 1994 and August 1996. METHODS: Dual energy X-ray measurement of bone density of femoral neck and lumbar spine, and venous blood sample taken just prior to the next injection of DMPA. MAIN OUTCOME MEASURES: Bone density of femoral neck and lumbar spine and serum oestradiol in relationship to years of DMPA use and duration of amenorrhoea. RESULTS: Most women (n=153) had serum oestradiol levels < 150 pmol/l. Despite this, the mean bone density of the lumbar spine compared with the population mean for women aged 20-59 years gave a Z score (95% CI) of -0.332 (-0.510 to -0.154). There was no significant difference in the mean density of the femoral neck from the normal population mean. CONCLUSION: Despite amenorrhoea and low serum oestradiol, this sample of long term DMPA users had bone density only minimally below the normal population mean. We therefore found no clinically important adverse effect on bone density and therefore no reason to recommend bone conserving measures, such as add-back oestrogen.

PIP: The effects on bone density of long-term depot medroxyprogesterone acetate (DMPA) use were investigated in a cross-sectional study of 185 clients 17-52 years of age at family planning clinics in Portsmouth and Manchester, England, who had been receiving contraceptive injections for 1-16 years (median, 5 years). Dual energy x-ray measurements of bone density of the femoral neck and lumbar spine, as well as venous blood samples, were taken prior to the women's next DMPA injection (1994-96). 153 women had serum estradiol levels under 150 pmol/l--the value considered adequate to maintain bone density. The mean bone density of the lumbar spine compared with the population mean for women 20-59 years old yielded a Z score of minus 0.332 (95% confidence interval, -0.510 to -0.154; p 0.001). There was a weak, nonsignificant correlation between lumbar spine Z score and years of DMPA use. Mean density of the femoral neck did not differ significantly from the normal population mean. There was no significant correlation between serum estradiol level and either bone density score. Overall, these findings provide no evidence that DMPA-induced amenorrhea places women at significant risk of further bone loss or that supplemental estrogen is required.

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BACKGROUND: To avoid the usual problems of multi-population correlation studies of air pollution and mortality, and for reasons of convenience, daily time-series mortality studies within single populations have recently become popular in air pollution epidemiology. Such studies describe how the short-term distribution of deaths relates to short-term fluctuations in air pollution levels. The regression-based risk coefficients from these acute-effects studies have been widely used to estimate the excess annual mortality within a population with a specified average level of air pollution. Such calculations are inappropriate. Since daily time-series data provide no simple direct information about the degree of life-shortening associated with the excess daily deaths (many of which are thought to be due to exacerbation of well-advanced disease, especially cardiovascular disease), such data cannot contribute to the estimation of the effects of air pollution upon chronic disease incidence and long-term death rates. Yet it is that category of effect that is of most public health importance. CONCLUSION: Such effects are best estimated from long-term cohort studies that incorporate good knowledge of local (or personal) exposure to air pollutants and of potential confounders. Time-series studies, properly evaluated, can identify the existence of acute toxic effects of transient peak levels of air pollution; they are thus useful for monitoring acute toxicity and for identifying the most noxious pollutants. However, to quantify the long-term health impacts of air pollution we cannot use acute-effects data.

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The study assessing menstrual problems and side effects associated with long-term TCu 380A intrauterine device (IUD) use in perimenopausal women is reported. Fifty perimenopausal TCu 380A IUD acceptors who had IUD inserted after age 40 and used IUD at least 36 months were recruited. The mean age of acceptors at time of insertion was 44.2 years with an average parity of two live births. The mean body weight at insertion was 62.13 kg. Most of the bleeding patterns were regular cycles. Intermenstrual bleeding and pelvic pain were side effects most often reported. No pregnancies, pelvic inflammatory disease, or IUD expulsions occurred during the follow-up period. This study suggests that the use of TCu 380A IUD in perimenopausal women is safe and effective.

PIP: Menstrual problems and side effects associated with long-term Copper T 380A use in perimenopausal women were investigated in a follow-up study of 50 Thai women who had the IUD inserted after 40 years of age (average, 44.2 years) and used the device for at least 36 months. All study participants had their IUD inserted at the family planning clinic of the Faculty of Medicine, Chulalongkorn University, in Bangkok, Thailand, and were followed at 6-month intervals. Their average parity was 2 live births. The numbers of women with irregular menstrual cycles at 12, 24, and 36 months after IUD insertion were 7 (14%), 11 (22%), and 15 (30%), respectively. Intermenstrual bleeding and pelvic pain--the most common side effects--were experienced by 15 (30%) and 9 (18%) women, respectively, during 36 months of follow up. No pregnancies, pelvic inflammatory disease, or IUD expulsions occurred and there were no significant changes in body weight or blood pressure. These findings suggest that TCu 380A use is both safe and effective up to menopause.

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To provide pharmacokinetic data for safety evaluation on prolonged treatment with Cyclofem, which contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate in 0.5 mL microcrystalline aqueous suspension, the pharmacokinetic profiles of MPA after single and multiple administration of this monthly injectable contraceptive were investigated in Chinese women. Nine healthy fertile women received Cyclofem based on a once-a-month regiment for up to 1 year. Blood samples were collected immediately prior to drug administration and on days 1, 3, 5, 7, 14, 21, and 28 after injection. After the 1st, 6th, and 12th injection, the maximum serum concentrations (Cmax) of MPA were observed on days 3.4 +/- 0.9, 4.3 +/- 2.2, and 3.7 +/- 2.6, respectively. Cmax of serum MPA during the 1st, 6th, and 12th treatment cycles were 3.75 +/- 1.27, 5.54 +/- 1.79, and 5.55 +/- 1.80 nmol/L, whereas the areas under the curve (AUC0-28 days) were 55.84 +/- 28.15, 95.45 +/- 26.56, and 98.81 +/- 21.84 nmol/L.day, respectively. There was significant interindividual variation in the pharmacokinetics of MPA after intramuscular injection of Cyclofem. No significant change was demonstrated in mean residence time (MRT) of MPA after single and multiple injection. There was a tendency of increase in Cmax and AUC0-28 days of MPA during the first 6 months of treatment, whereas no further enhancement was found between the 6th and 12th injection (p > 0.05). Peak levels of estradiol (E2) observed in Cyclofem users were within the normal range of the preovulatory phase. Results of this long-term study suggest that no drug accumulation occurred after repeated administration of Cyclofem in the Chinese women.

PIP: To provide pharmacokinetic data for a safety evaluation of long-term use of the monthly injectable Cyclofem (25 mg of medroxyprogesterone acetate (MPA) and 5 mg of estradiol cypionate), 9 fertile Chinese women 27-34 years of age were enrolled in a 12-month clinical study. Serum samples were collected immediately prior to drug administration and on days 1, 3, 5, 7, 14, 21, and 28 after monthly injection. After injections 1, 6, and 12, maximum serum MPA concentrations were observed on days 3.4 +or- 0.9, 4.3 +or- 2.2, and 3.7 +or- 2.6, respectively. Maximum concentrations of serum MPA during treatment cycles 1, 6, and 12 were 3.75 +or- 1.27, 5.54 +or- 1.79, and 5.55 +or- 1.80 nmol/l, respectively, while the corresponding areas under the curve were 55.84 +or- 28.15, 95.45 +or- 26.56, and 98.81 +or- 21.84 nmol/l per day. There was significant interindividual variation in the pharmacokinetics of MPA after intramuscular injection. No significant change was recorded in mean MPA residence time after single and multiple injection. Noted was a trend of increases in MPA maximum serum concentration and areas under the curve during the first 6 months of treatment, followed by no further enhancement in the last 6 months. Peak estradiol levels were within the normal range of the preovulatory phase. These findings suggest that long-term Cyclofem use is not associated with drug accumulation. As a safe, highly effective formulation, Cyclofem offers women around the world yet another contraceptive choice.

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OBJECTIVE: The present study examined whether physical abuse functions as an additional risk factor for adolescent psychopathology after other important known risk factors are controlled for. METHOD: The authors recruited 99 adolescents aged 12 to 18 years directly from the New York State Department of Social Services after official documentation of physical abuse. The abused adolescents were compared to 99 nonabused adolescents matched for age, gender, race, and community income. Diagnostic interviews and measures of selected risk factors for psychopathology were administered to the adolescents and their parents and then entered into a multiple logistic regression model testing the added risk contributed by physical abuse to adolescent psychopathology. RESULTS: Physical abuse added significantly to other risk factors in accounting for lifetime diagnoses of major depression, dysthymia, conduct disorder, drug abuse, and cigarette smoking. Physical abuse also contributed significantly to prediction of current adolescent unipolar depressive disorders, disruptive disorders, and cigarette smoking. CONCLUSIONS: Since physically abused adolescents are at greater risk for the development of psychiatric disorders, recognition of adolescent abuse and the provision of psychiatric and substance abuse services may reduce morbidity.

PIP: The association between physical abuse of adolescents and adolescent psychopathology was investigated in a case-control study conducted in Long Island, New York (US). 99 White adolescents 12-18 years of age identified from the New York State Department of Social Services Central Register for Child Abuse in 1989-91 and 99 nonabused adolescents matched for age, gender, race, and community income were enrolled. Diagnostic interviews and measures of selected risk factors for psychopathology were administered to the adolescents and their parents and then entered into a multiple logistic regression model testing the added risk contributed by physical abuse. Physical abuse added significantly to other risk factors in accounting for lifetime diagnoses of major depression, dysthymia, conduct disorder, drug abuse or dependence, and cigarette smoking. Physical abuse also contributed significantly to the prediction of current adolescent unipolar depressive disorders, disruptive disorders, and cigarette smoking. These findings underscore the importance of increased identification of physically abused adolescents so that mental health and substance abuse services can be provided.

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PIP: A case report presented by a US psychoanalyst suggests that the trauma of reproductive loss, such as miscarriage of a wanted pregnancy, can trigger suppressed feelings associated with an earlier induced abortion. The patient entered psychoanalysis when she was a 24-year-old graduate student to address relationship problems. As a 19-year-old college student, she became pregnant and chose to have an induced abortion because she was not ready to make a permanent commitment to her boyfriend or to provide properly for a child. She reported feeling grateful at the time that motherhood was not imposed on women as punishment for being sexually active and that childbearing was a free choice. The patient married during psychoanalytic treatment and decided she wanted to have a child. She experienced a hydatiform molar pregnancy, following which memories of the abortion 10 years earlier began to surface in the analysis for the first time. Her grief about the recent pregnancy loss melded with emotions about the earlier abortion. Through the analytic relationship, the patient was able to experience and express this sadness. This case underscores the need for psychotherapists to ensure that the political importance of protecting women's right to reproductive choice does not obstruct the exploration of complex emotions that may be associated with a voluntary induced abortion.^ieng

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There is good evidence that estrogens and progestogens have an important effect on bone metabolism. This article explores the relationship between oral contraceptive (OC) use and fractures occurring at various sites among the 17,032 participants in the Oxford-Family Planning Association contraceptive study, which now includes information accumulated during 310,000 woman-years of observation between 1968 and 1994. In total, 1308 women suffered at least one fracture during the follow-up period, which was largely confined to premenopausal years. When all fractures were combined, there was a modest, but highly significant trend (p < 0.001) of increasing risk with total duration of oral contraceptive use. In addition, there was statistically significant heterogeneity (p < 0.01) when overall fracture rates were examined in relation to recency of oral contraceptive use during the premenopausal lifespan. The highest relative risk (1.3, 95% CI 1.1-1.5) was for current or recent oral contraceptive users; however, viewed as a whole, no clear pattern of risk was apparent. Examination of the data for individual fracture sites (including the lower end of the radius/ulna) did not provide any evidence of a protective effect of oral contraceptive use. These results are closely similar to those reported from the Royal College of General Practitioners Oral Contraception Study in 1993.

PIP: Estrogens and progestogens have an important effect on bone metabolism. The present study explored the relationship between oral contraceptive (OC) use and bone fractures in the cohort of 17,032 English and Scottish participants in the Oxford-Family Planning Association contraceptive study (1968-94). The analysis was based on the calculation of woman-years of observation terminated by referral for fracture or release from follow-up due to death, emigration, or short-term pill users reaching age 45 years. A total of 1308 women experienced at least one fracture during 310,000 woman-years of observation and there was a significant (p 0.001) positive relationship between age and fracture risk. Most common were fractures of the radius/ulna, tarsal/metatarsal bones, and ankle. When all fractures were combined, there was a significant (p 0.001) increasing risk with total duration of OC use. Also observed was a significant (p 0.01) heterogeneity when overall fracture rates were examined in relation to recency of OC use during the premenopausal lifespan. The highest relative risk (1.3; 95% confidence interval, 1.1-1.5) was recorded among current or recent OC users. There was about a 20% increase in the overall risk of fracture in women who had used OCs at any time compared with never-users. Overall, however, no clear pattern of risk emerged. These results are similar to those reported in the 1993 Royal College of General Practitioners OC Study. It is assumed that the increased fracture risk in OC users results from life-style characteristics of such women rather than a direct effect of OCs on bone.

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The aim of the present study was to investigate whether maternal, antenatal and perinatal complications are associated with adolescent or young adulthood suicide in offspring. Cases consisted of individuals, aged 15-22 years, born in New York City and committing suicide in New York City between 1985 and 1991 (n = 189). Two controls were selected for each case, constituting the hospital birth immediately preceding and following that of the case, matched with the case with regard to sex and ethnicity. Cases were compared with controls using an index that summed a range of maternal, antenatal and perinatal complications and also with regard to the frequency of individual complications. In the total sample, cases and controls did not differ either in the mean number of all complications combined or in the proportions with specific complications. This lack of association between complications and outcome also obtained in separate analyses by sex, ethnicity, socio-economic status and age at suicide. These results fail to replicate the findings of two previous reports implicating maternal, antenatal and perinatal complications in risk of youth suicide. At present, epidemiological evidence that adverse reproductive events increase the risk for suicide in offspring remains inconclusive.

PIP: The hypothesis that maternal, antenatal, and perinatal complications are associated with adolescent and young adult suicide in offspring was investigated in a case-control study conducted in New York City, New York (US). 189 youths 15-22 years old, born in New York City and committing suicide in New York City in 1985-91, served as cases. Two sex- and ethnicity-matched controls, constituting the hospital birth immediately before and after that of the case, were enrolled for each case. Cases and controls did not differ either in the mean number of all maternal, antenatal, and perinatal complications combined or in the proportions with specific complications. This lack of association between complications and outcome persisted in separate analyses by sex, ethnic group, socioeconomic status, and age at suicide. Two previous studies found significantly elevated suicide rates in youth who experienced respiratory distress at birth lasting more than 1 hour and whose mothers had a chronic illness during pregnancy or did not enter prenatal care before 20 weeks gestation.

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