Paediatric drug use with focus on off-label prescriptions at Swedish hospitals - a nationwide study.

AIM: To perform a nationwide investigation of paediatric drug use at Swedish hospitals, including an analysis of off-label drug use. METHODS: All paediatric hospitals in Sweden were invited to register all prescriptions to children, aged between 0 and 18, during two separate 2-day-periods in 2008. Data were reported and analysed with respect to licence status and proportion of and reasons for off-label drug use. RESULTS: Data on 11,294 prescriptions to 2947 paediatric patients were received. Drugs associated with pain relief, infection, prematurity, nutrition and surgery or anaesthesia were most commonly used. Paracetamol was the most frequently used drug on-label and also among the most commonly used off-label drugs. Nearly half (49%) of all administered prescriptions concerned unlicensed drugs, off-label drugs or extemporaneously prepared drugs. The corresponding rate among neonates was 69%. Lack of paediatric information in the Summary of Product Characteristics was the main reason for off-label classification. CONCLUSIONS: Paediatric off-label drug use is common at Swedish hospitals, and nearly half of all prescriptions were not documented for use in children. The findings emphasize a need for paediatric clinical studies as well as compilation of existing clinical experience and scattered evidence, particularly for drug treatment in infants and neonates.

Paediatric drug use with focus on off-label prescriptions in Swedish outpatient care--a nationwide study.

AIM: To determine drug prescription and proportion of off-label dispensing in the Swedish paediatric outpatient population. METHODS: All dispensed outpatient prescriptions to children aged 0 < 18 years as well as the proportion of off-label drug use during 2007 were analysed using data from the Swedish Prescribed Drug Register. RESULTS: In total, 2.19 million drug prescriptions of 898 different drug substances were dispensed to paediatric patients, and of those substances, 64% had been dispensed off-label at least once. The overall off-label rate of all prescriptions was 13.5%, among which topical drugs as well as sex hormones were the most commonly prescribed off-label drugs. More than half of all children in Sweden had received at least one prescribed drug in 2007. CONCLUSIONS: There is a high prescribing of medicines to children in outpatient care in Sweden with a considerable amount of off-label prescriptions. Topically administered drugs, sex hormones, antidepressants, hypnotics, cardiovascular drugs and nonsteroidal anti-inflammatory drugs were commonly prescribed off-label.

The impact of age and intrauterine contraception on the clinical course of pelvic inflammatory disease.

BACKGROUND: The aim of the study was to investigate the clinical course of pelvic inflammatory disease (PID) and factors that could predict failed conservative treatment of PID. Additionally, the study aimed to examine the role of age and intrauterine device (IUD) use on the severity of PID. METHOD: Fifty-one women admitted to hospital with the diagnosis of acute PID were recruited. Of those, 17 patients were subsequently operated because of failed conservative treatment. All women underwent careful examination and completed a questionnaire at admission. Their clinical course was followed and the clinician responsible for the patient completed forms at admission and at discharge. Two groups were established retrospectively, those who were treated conservatively and those who underwent surgery. The outcome results were analyzed with regard to IUD use, duration of IUD use (>or=5 or <5 years), and with regard to age below or above 35 years. All data were analyzed using the statistical package SAS. A p value <0.05 was considered significant. RESULTS: Women who subsequently underwent surgical treatment were significantly older and significantly more frequently, current IUD users. There was no significant difference with regard to other socio-demographic characteristics. Women who subsequently underwent surgery had significantly more frequent complaints of severe abdominal pain, elevated body temperature, symptoms of peritoneal irritation, and appearance of adnexal mass. No differences were found between groups with regard to anaerobic microbiological findings, nor with regard to the finding of Actinomyces. IUD use and age >or=35 were found to be highly significant risk factors for surgery in patients with PID. CONCLUSION: Age over 35 years and IUD use, independently of each other, were factors strongly associated with an increased risk of surgery for PID as a result of failed conservative treatment.

Microbiology profile in women with pelvic inflammatory disease in relation to IUD use.

OBJECTIVE: To study the microbial characteristics of patients with pelvic inflammatory disease (PID) and the possible impact of an intrauterine device (IUD) on the microbial environment in women presenting with PID. METHODS: Case-control study, investigating 51 women with acute PID and 50 healthy women. Endocervical specimens for microbiological investigation were obtained at gynaecological examination. RESULTS: IUD users with PID had significantly more Fusobacteria spp. and Peptostreptococcus spp. than non-IUD users with PID. The finding of combinations of several anaerobic or aerobic microbes was associated with a significantly increased risk of PID and with complicated PID. In IUD users, the combinations of several anaerobic/aerobic microbes were associated with an increased risk of PID, irrespective of duration of IUD use. Long-term IUD use appeared to be associated with an increased risk of a PID being complicated. CONCLUSION: The finding of several anaerobic or aerobic microbes appears to be associated with PID in users of IUD.

Contraceptive practices and intentions of Ukrainian women.

OBJECTIVES: This study was undertaken to investigate contraceptive practices and factors behind contraceptive preferences among Ukrainian women attending for abortion or gynecological health check-up. METHODS: Women attending for abortion (n = 919) and healthy non-pregnant women (n = 297) were studied by an anonymous 192-item self-questionnaire in a hospital-based unmatched case-control design. RESULTS: The average number of abortions per woman rose with age to 4.6 in the abortion group and 2.4 abortions in the non-pregnant group. In the abortion and non-pregnant groups, no contraceptive use during the past year was reported by 27% and 20% and at the time of conception or during the previous month, by 61% and 51%, respectively. Nevertheless, no intention to use contraception in the future was reported by 15% and 8% of women, respectively. A history of previous childbirth (odds ratio (OR) = 1.8), at least two induced abortions (OR = 1.7) and sexual education obtained from literature (OR = 1.8) were associated with preference to use modern contraceptives. Intention to use no contraception in the future was associated with giving no answer about acceptance of abortion as a birth control method (OR = 5.4), uncertainty whether to use abortion or an intrauterine device in a situation of choice (OR = 1.8), low income (OR = 1.9) and no answer about housing situation (OR = 3.9). Lack of experience with contraception reduced the intention to use any method in the future. CONCLUSIONS: Better reproductive education/information and economic incentives could contribute to a change from abortion to use of contraception.

Ukrainian medical students' experiences, attitudes, and knowledge about reproductive health.

In a 1999 classroom survey of sexual behavior among 689 1st-year medical students at Donetsk State Medical University, Ukraine, 59% of the women and 83% of the men revealed they had "ever" had sexual intercourse. The mean age of first intercourse was 15.7 years for the men and 16.6 years for the women. Thirty-two percent of the students reported they did not use contraceptives at their first intercourse, and 19% said they used no contraceptives at their most recent coitus. Condoms were the most frequent means of contraception, followed by coitus interruptus. Less than 5% used oral contraceptives, and 73% of students reported being afraid to use them. About 6% of the students reported they had had sexually transmitted infections (STI) and 10% had had an abortion. Improving knowledge concerning unwanted pregnancies and STI among Ukraine's future health providers may contribute to improving reproductive health issues in general in Ukraine.

Effects of oral contraceptives on breast epithelial proliferation.

The association between oral contraceptive (OC) use and breast cancer is not fully understood. Estrogen is a known mitogen to breast epithelial cells, but there is still a controversy about the effect of added progestogens. Fine needle aspiration (FNA) biopsies were used to assess epithelial proliferation in normal breast tissue from 106 healthy premenopausal women with and without oral contraceptives. In 26 women biopsies were performed before and after 2 months of OC use. Proliferation, expressed as percentage of Ki-67/MIB-1 positive cells, was correlated to endogenous progesterone, androgenic/anabolic compounds and exogenous progestogen. We found a higher proliferation (p = 0.03) in OC users compared to non users, with mean values of 4.8% and 2.2%, respectively. There was a positive correlation between proliferation and progesterone levels in non-users and with serum levonorgestrel concentrations in women using OCs containing this progestogen (rs = 0.43, p = 0.02). Women using OCs had significantly lower serum androgen levels compared to naturally cycling women and free testosterone levels displayed an inverse relation to breast epithelial proliferation. There was a marked variation in the response to exogenous sex steroids. In certain women after 2 months of OC use, the percentage of MIB-1 positive cells was as high as 40-50%. The results add to the growing evidence that progestogens may be mitogenic in breast tissue. Increased proliferation during hormonal contraception should be regarded as an unwanted and potentially hazardous side effect. Efforts should be made to define hormonal contraceptive regimens which minimize breast epithelial proliferation and to identify those women with the most pronounced proliferative response.

Factors associated with pregnancy termination in Ukrainian women.

OBJECTIVES: To study differences in social and demographic characteristics between women undergoing an induced abortion and antenatal care attendants in the Ukraine. DESIGN: Hospital-based unmatched case control study. METHODS: From a survey including 1,694 women of fertile age, who attended five women's clinics in the Donetsk region, Ukraine, we studied those who came for termination of pregnancy (n = 919) and for antenatal care (n = 478). The data were obtained through an anonymous self-questionnaire. From the 192-item questionnaire questions dealing with social and demographic characteristics, previous pregnancy experience, and attitude towards abortion were analyzed. Multiple logistic regression was used to analyze the risk of pregnancy termination. RESULTS: Termination of pregnancy was associated with being single (OR = 11.8). Both previous childbirth and previous induced abortion were other determinants as well as being younger than 19 years old (OR = 3.8), having a positive attitude towards abortion (OR = 2.7), and sharing apartment with parents (OR = 1.9). A higher risk for an induced abortion was found among women with a history of previous induced abortion(s). Neither income nor educational level was identified as a risk factor for pregnancy termination. CONCLUSION: This study demonstrated major social and demographic differences between women attending for abortion and antenatal care patients, and highlights some of the factors influencing the decision to terminate a pregnancy.

Combined oral contraceptives do not increase the risk of back and pelvic pain during pregnancy or after delivery.

OBJECTIVES: To elucidate whether the duration of previous use of combined oral contraceptives (COC) is associated with disabling back or pelvic pain during pregnancy and pain persisting eight months after delivery. METHODS: Questionnaires were distributed to a group of women at 36 weeks of pregnancy and eight months after their delivery. There were no exclusion criteria. Disabling pain was defined as moderate or severe pain restricting physical activity. Multiple logistic regression analysis of disabling pain during pregnancy and persistent pain after delivery comprised the duration of COC use adjusted for age, pain in a previous pregnancy and a history of back pain when not pregnant. RESULTS: The study comprised 161 women. Pain during pregnancy was classified as disabling in 57 of the women (35%), pain in a previous pregnancy being a risk factor, odds ratio (OR) 5.0 (95% CI 2.1; 12.1), whereas no association was found with the duration of COC use. Persistent pain eight months after delivery was reported by 41 women (26%), risk factors being a history of back pain when not pregnant; OR 7.5 (2.8; 19.5), disabling pain in the recent pregnancy; OR 5.0 (1.9; 13.4), and short use of COC; 0-<1 year; OR 4.2 (1.3; 12.9), 1-<5 years; OR 4.6 (1.5; 14.4) (reference=>10 years). CONCLUSION: The results indicate that non- or short term users of COC have an increased risk of persistent pain after delivery compared to long term users. No association was found between the duration of COC use and back or pelvic pain during pregnancy.

[Fertility and contraception in women older than 40 years]. / Fruktsamhet och preventivmedel efter 40.

Women in their later reproductive years constitute a large proportion of contraceptive users. Although increasing age is accompanied by a general decline in fecundity, each individual needs to know her own risk or possibility of becoming pregnant and when it is safe to stop using contraceptives. Women over 40 need special consideration since pregnancy and childbirth is sometimes associated with higher health risks both for mother and infant. Women over 40 are more likely than younger women to have medical problems, menstrual disorders and previous experience that may affect their choice and use of contraceptive methods. Recommendations for counselling, health screening and choice of contraceptive method in women in their later reproductive years are given.

Health effects of long-term use of the intrauterine levonorgestrel-releasing system. A follow-up study over 12 years of continuous use.

BACKGROUND: This report comprises women from one center, who all participated in a larger European multi-center study, which included 2758 healthy women, of whom 1821 were randomly allocated to the levonorgestrel-releasing intrauterine system (Lng-IUS) and 937 to a copper-IUD (Nova-T). At the end of the 5 year study period, 109 of the 300 women, who originally were allocated to the Lng-IUS at this center, were still using the Lng-IUS. The women were offered the opportunity to continue the Lng-IUS and 100 women chose to do so. After a total period of almost 7 years of continuous use, a second Lng-IUS was offered and 82 of the women chose to start a second segment of Lng-IUS use. After another 5 years, 69 of the women were fitted with their third Lng-IUS. METHODS: These 82 women were examined yearly throughout the study period and bleeding pattern, hemoglobin, weight, blood-pressure, general well-being and intercurrent disease were analyzed to assess long-term effects. RESULTS: No pregnancy occurred during the follow-up. One case of partial expulsion occurred and one case of pelvic inflammatory disease. Seventy-seven percent of the women did not report any health problems at all during the entire follow-up period of 13 years. At the end of the second period with the Lng-IUS, 60% reported amenorrhea, 12% infrequent, scanty bleeds and 28% regular, scanty bleeds. As a consequence, the hemoglobin values increased, with a mean increase, after 12-13 years, being 1.35 g/dl. Blood pressure increased slightly and body weight increased with a mean increase of 0.49 kg/year. Seven women became postmenopausal during the follow-up and started estrogen replacement therapy with the Lng-IUS in situ. CONCLUSIONS: This follow-up study suggests that the Lng-IUS remains a safe and effective method of contraception, allowing women prolonged relief of menstrual problems, and for women in their late reproductive years, offering a convenient and bleeding-free transition into the menopause.

Oral contraceptives and compliance: reaction to cardiovascular alarm among users.

The effectiveness of oral contraceptives (OC) is dependent on correct daily intake as well as continuous use. The latest cardiovascular alarm in 1995 led to discontinuations, presumably due to concerns about the long-term safety of OCs. The aim of this study was to investigate women's experiences and concerns about OCs in general as well as after the latest cardiovascular alarm. In 1993 and 1996, questionnaires were offered to 645 and 644 consecutive women visiting a midwife or a gynecologist at eleven family planning clinics in order to get their first prescription of oral contraceptives or to renew their prescription. The study was carried out in Uppsala, a city in Sweden with 180000 inhabitants. In 1993, 95%, answered the questionnaire and in 1996 the corresponding figure was 92%. Change of brand was common and increased from 38% in 1993 to 44% in 1996. Mild side-effects were reported by about 25%. Concerns about oral contraceptives increased from 36% to 41% (p < 0.01), particularly regarding the risk for thrombosis. Fewer than 1% expressed this concern in 1993 but 29% did so in 1996. Negative media coverage leads to increased concerns and declining confidence among users of oral contraceptives and has to be met by adequate oral and written information by the counsellor.

Evaluation of an STD-prevention program for Swedish university students.

The authors evaluated a sexually transmitted disease (STD)-prevention program that combined a mass media campaign with peer education. The program was designed to increase Swedish university students' knowledge about STDs, improve attitudes toward condom use, and tell students where to get an STD checkup. Preintervention and postintervention postal questionnaires wer used with an intervention group and two types of control groups. Responses ranged from 32% to 67% for the randomly selected students and from 93% to 99% for classroom and clinic participants. The intervention was noticed by a majority of the students (85-98%) and discussed by 43% to 57%; more women than men observed and discussed the campaign. Knowledge about STDs, where to turn for STD checkups, and the intention of having an STD checkup increased. Attitudes toward condom use were equally positive before and after the intervention. Although it was successful in attracting attention and leading to discussion of STD prevention, the campaign did not encourage students to have an STD checkup.

Perforations with intrauterine devices. Report from a Swedish survey.

This survey comprised 50 consecutive perforations occurring with intrauterine devices (IUD) reported to the National Patient Insurance Scheme Register during 1990 to 1993. All 50 women were parous and > 20 years of age at the time of IUD insertion. Forty-two (84%) of the IUD were inserted by a midwife and eight by a gynecologist. A total of 45 women (90%) had their IUD inserted < 1 year after a full-term pregnancy and 31 women (62%) had their IUD inserted < or = 12 weeks after delivery. Of the 50 women, 27 (54%) reported that they were breastfeeding at the time of IUD insertion. No particular IUD was overrepresented in relation to its share on the market. In 31 cases (62%), severe pain at insertion and during the first 24 h was recorded. In 14 women (28%), the perforation was diagnosed early (i.e., within 1 month of insertion) and in 36 women (72%), the perforation was diagnosed > 1 month after insertion. Lower abdominal pain was the most frequent symptom at early diagnosis but in two cases, the main symptom was heavy bleeding. Among the 36 women in whom the perforation was discovered more than 1 month after insertion, the diagnosis was made when an unexpected pregnancy occurred in 20 women (56%). In 15 cases, the IUD strings were not visible during pelvic examination at a routine check-up, which led to efforts to locate the IUD. Thirty-two women (64%) underwent laparotomy for removal. We conclude that lactating women seem to be a risk group for perforation and that a national register of IUD perforations could provide a better means of quality control.

Emergency contraception: the user profile.

UNLABELLED: Emergency contraception (EC) has recently become available, accepted and widely used in Sweden but little is known about the characteristics and background factors of women requesting EC. METHODS: During a four-month period, consecutive women (n = 762) visiting family planning clinics to request emergency contraception filled out a questionnaire about their current need for EC. RESULTS: The user of emergency contraception was typically a nulligravid young woman (83%) but 13% had a previous history of at least one induced abortion and 41% had given birth in the past. One out of four had used EC before, and of these 20% more than once. Condom breakage was the major reason for the current need for EC but as many as 37% had not discussed the need for contraception prior to intercourse. Friends were the most important source of knowledge about EC. CONCLUSION: Women requesting emergency contraception could be anyone and emergency contraception is used to compensate for contraceptive failure in order to prevent unwanted pregnancies.