Utilization of carbetocin for prevention of postpartum hemorrhage after cesarean section: a randomized clinical trial.

PURPOSE: A randomized study involving pregnant women was conducted to compare the effectiveness of a single intravenous (IV) injection of carbetocin with that of a standard 2-h oxytocin IV infusion with respect to intraoperative blood loss in the prevention of uterine atony after cesarean section (CS). The two treatments also were compared for safety and ability to maintain adequate uterine tone and to reduce the incidence and severity of postpartum hemorrhage (PPH) in women at risk for this condition. METHODS: Between 1 September 2007 and 5 January 2008, we enrolled 104 patients with at least one risk factor for PPH undergoing CS in a randomized, controlled clinical trial. We compared the effect of a single 100 microg IV dose of carbetocin with that of a standard 2-h ten international units (IU) IV infusion of oxytocin. The primary outcome was the proportion of patients requiring additional oxytocic intervention for uterine atony. Fiftytwo women received 100 microg carbetocin IV immediately after placental delivery, while 52 women received 10 IU oxytocin IV infusion. Complete blood count was collected at entry and 24 h postpartum. All outcome measures, including the need for additional uterotonic agents or uterine massage, and blood loss, were analyzed using chi-square, Fisher exact, and Student's t tests. RESULTS: A single 100 microg IV injection of carbetocin was as effective as a continuous 2-h infusion of oxytocin in controlling intraoperative blood loss after placental delivery. Mean blood loss after carbetocin administration was 30 ml less than after oxytocin administration (P = 0.5). The percentage of patients with blood loss < or =500 ml was greater with carbetocin (81 vs. 55%; P = 0.05). Carbetocin enhanced early postpartum uterine involution. The fundus was below the umbilicus in more patients who received carbetocin at 0, 2, 6, and 24 h on the ward (P < 0.05). The main additional uterotonic agent used was a further administration of oxytocin (20 IU in physiological solution 500 ml at an infusion rate of 200 ml/h). In the carbetocin group, 20 of the 52 women (38.4%) required at least one uterine massage compared to 30 of the 52 women (57.7%) in the oxytocin group (P < 0.01). Overall, uterotonic intervention was clinically indicated in two of the women (3.8%) receiving carbetocin compared to five of the women (9.6%) given an IV oxytocin infusion (P < 0.01). The odds ratio of treatment failure requiring oxytocic intervention was 1.83 (95% confidence interval, CI, 0.9-2.6) times higher in the oxytocin group compared with the carbetocin group. CONCLUSIONS: Carbetocin makes possible to obtain, with a single IV injection, results equivalent to those of oxytocin on the maintenance of uterine tonicity and the limitation of blood losses, in the peri- and in the post-operative period, during a delivery by CS. It has in addition a comparable tolerance. Even in our series adverse events are practically of the same type and similar frequency in both study groups. Thus, the effectiveness of carbetocin consists, thanks to its long half-life, on an unique injection, whereas oxytocin requires repeated injections or a perfusion of several hours, with a variability of the administered doses.

Uptake of cervical cancer screening among the migrant population of Prato Province, Italy.

OBJECTIVE: To determine the level of participation in cervical cancer screening among the migrant population of Prato Province, Italy. METHODS: A retrospective cross-sectional study was conducted using data for women aged 25-64 years who were resident in one of the municipalities of Prato Province and had received at least one invitation to undergo a cervical cancer screening test. Data were extracted from both the Local Health Unit Serviceable Registry and cervical cancer screening archives for the period July 1, 2004, to June 30, 2007. RESULTS: Of the 69 459 residents eligible for cervical cancer screening, 7339 (10.6%) did not have Italian citizenship. Adherence with cervical cancer screening among the migrant population was lower than that of the Italian resident population: uptake increased from 52.4% in 2004 to 57.3% in 2007 among the Italian resident population, but decreased from 31.4% to 28.2% among migrants. CONCLUSION: The migrant population of Prato Province has decreased adherence with cervical cancer screening.

Cervical cancer screening: A never-ending developing program.

With the term "oncological screening", we define the overall performances made to detect early onset of tumors. These tests are conducted on a population that does not have any signs or symptoms related to a neoplasm. The whole population above a certain age, only one sex, only subjects with a high risk of developing cancer due to genetic, professional, discretionary reasons may be involved. Screening campaigns should be associated, when risk factors that can be avoided are known, with campaigns for the prevention of cancer by means of suitable behavior. The goal of cancer screening cannot however be limited to the diagnosis of a greater number of neoplasms. Screening will be useful only if it leads to a reduction in overall mortality or at least in mortality related to the tumor. Screening should then allow the diagnosis of the disease at a stage when there is a possibility of healing, possibility that is instead difficult when the disease is diagnosed at the appearance of signs or symptoms. This is the reason why not all campaigns of cancer screening have the same effectiveness. In Italy, every year there are about 150000 deaths due to cancer. Some of these tumors can be cured with a very high percentage of success if diagnosed in time. Cervical cancer can be diagnosed with non-invasive tests. The screening test used all over the world is Papanicolaou (Pap) test. This test may be carried out over the entire healthy population potentially exposed to the risk of contracting cancer. Public health has begun the screening campaigns in the hope of saving many of the approximately 270000 new cases of cancer reported each year. Screening is done following protocols that guarantee quality at the national level: these protocols are subject to change over time to reflect new realities or to correct any errors in the system. A simplified sketch of a possible route of cancer screening is as follows: (1) after selecting the target population, for example all women between 25 and 64 years (in the case of monitoring of cervical cancer), an invitation letter with the date and time of the appointment, planned according to the acceptance capacity of the hospital, is sent to all individuals; (2) an examination, which depending on the individual and the type of cancer to be monitored, for example, can be a Pap smear, is performed and the patient can go home; (3) once available the results of examinations, if negative, they shall be communicated to the person concerned that will be notified by mail and will be recalled for a second test at a few years of distance, in the case of non-negativity, instead, the patient is contacted by telephone and informed of the need to carry out further examinations: it is said that the patient is in the "phase two" of the screening pathway; (4) in phase two, reached by only a small portion of the interested parties (usually less than 3%-5%), more in-depth tests are carried out, which, depending on the individual and the type of cancer, can be: cytological and colposcopic examinations, the removal of a fragment of tissue (biopsy) and subsequent histological examination, additional tests such as ultrasound, radiography, or others such as computerized tomography, magnetic resonance imaging, positron emission tomography, etc., in case of negativity, the concerned person will be called for new control tests at a a few years of distance, in case of non-negativity, it will be proposed instead an oncologic therapeutic plan and/or surgery to treat the diagnosed tumor; and (5) once the treatment plan is completed, the individual enters the follow-up protocol, which is monitored over time to see if the tumor has been completely removed or if instead it is still developing. Cervical cancer is undoubtedly the most successful example of a cancer screening campaign. Paradoxically, its effectiveness is one of the strongest reasons to criticize the usefulness of vaccination against human papillomavirus (HPV) in countries where the screening service with Pap test is organized in an efficient manner. Cervical cancer screening protocols are directed to sexually active women aged 25-64 years: they provide the Pap test performed by examining under a microscope or by staining with a specific "thin prep" the material taken from the cervix with a small spatula and a brush. It is recommended to repeat the test every two or three years. It is important to emphasize that women vaccinated against HPV must continue the screening with Pap test. Although some screening programs (e.g., Pap smears) have had remarkable success in reducing mortality from a specific cancer, any kind of screening is free from inherent limitations. The screening methods are in fact applied to large parts of the apparently healthy population. In particular, the limits for certain cancers may be as obvious as to prohibit the introduction of an organized screening program. Potential limitations of organized screenings are basically of two types: organizational and medical. The limits of organizational type relate to the ability of a program to recruit the whole target population. Although well organized, a screening program will hardly be able to exceed a coverage of 70%-80% of the target population, and in fact the results of the current programs are often much smaller. The limits of medical type are represented by the possibility of reducing the overall mortality, or specific mortality, using a specific screening campaign.

GnRH antagonists.

Ovarian stimulation is an important step in the success rate of in vitro fertilization (IVF) allowing multiple follicular growth, several oocytes and consequently more embryos. The combination of GnRH-antagonists (GnRH-ant) and gonadotrophins is now available for clinical use and represent a valid alternative to classical protocol with GnRH agonist. GnRH-antagonists induce a direct block of GnRH receptor with a rapid decrease in LH and FSH, preventing LH surge. Two protocols has been designed for assisted reproduction technology (ART) treatment: multiple-dose protocol and a single-dose. Both protocols are simply, efficacious, started in the late follicular phase and do not have side effects. A review of GnRH-antagonist applications in ART cycles are presented. Smaller doses of gonadotrophins, shorter stimulation period and lower ovarian hyperstimulation syndrome (OHSS) incidence are reported in literature using GnRH-antagonist compared to agonist. Triggering of ovulation, the use in polycystic ovarian syndrome (PCOS) and poor reponders patients are other interesting indication. Regarding to pregnancy rate and potentially adverse effects of drugs on endometrium or implantation needed more data.

Prevention of cerebral palsy during labour: role of foetal lactate.

OBJECTIVES: Intrapartum foetal monitoring goal is to prevent foetal asphyxia and its most severe consequence: cerebral palsy (CP). In this paper we describe the detection methods and the criteria needed to assess asphyxia during labour for preventing CP. Foetal cerebral damage assessment is considered from the medical-legal point of view. CP represents the most frequent pathology of childhood related to pregnancy and childbirth with an incidence of 0.2% in children born alive. It is clinically regarded as the result of a spectrum of diseases due to damage or to faded development of the nervous system which generally appears at the time of the first stage of intra-uterine growth or depends on problems arising at birth. The goal of our analysis is to recall the various moments in which this event can take place and, if possible, the moment and the degree of the event of asphyxia and its effect on foetal conditions, in order to control and treat it. STUDY DESIGN: One hundred and eighty-eight fetuses were evaluated by means of Apgar score, intrapartum cardiotocography, observation of the presence of meconium stained amniotic fluid, and clinical features of distress at birth. Lactate concentrations were measured during labour and at delivery in blood samples obtained from the foetal presenting part (foetal scalp) and from the umbilical cord with the use of a rapid electrochemical technique. RESULTS: Evidence of clinical foetal distress was not related to the severity of asphyxia. An increased lactate level was found in asphyctic infants and a clear correlation between lactic acidosis and foetal distress was documented. Low Apgar scores were observed in infants with moderate or severe asphyxia at delivery. Scalp lactate correlated significantly with umbilical artery lactate (P = 0.49, 0.01), but with neither Apgar score at 1 min (R = -0.21, ns) nor at 5 min (R = -0.11, ns). Lactate concentration was higher in case of instrumental delivery compared to spontaneous delivery (P = 0.0001). No perfect correlation was found between lactate level and neonatal outcome, but there were not a significant number of neonates with immediate complications. The rate of instrumental delivery in the distress group was significantly higher than in that of the healthy fetuses (P < 0.01), so spontaneous labour was less frequently associated with foetal distress than instrumental delivery (P < 0.01). In the distress group, severe variable decelerations were generally recorded in the second stage of labour. The incidence of neonatal Apgar score /=45 min, compared with a shorter active second stage, and acidaemia at birth implied larger arterial-venous lactate differences (P < 0.001). The presence of foetal lactate at crowning was also significantly associated with the level of umbilical arterial-venous lactate difference (P = 0.03). CONCLUSIONS: Analysis of the fetus should start with the assessment of lactates and acid-base balance. The method which revolutionized the techniques of foetal monitoring is undoubtedly represented by cardiotocography. However, likely most of neurological outcomes are not correlated with a perinatal event or with peripartum asphyxia. Approximately 10% of cases of CP would actually be due to perinatal asphyxia, and this percentage approaches approximately to 15% if we consider only newborns at term. This again confirms the weak association of a causal relationship between asphyxia and CP. In addition, available foetal suffering markers are vague and allow to identify only less than half of the effective cases of newborns which will develop CP.