Impact of an educational intervention on patient safety culture among gynecology-obstetrics' healthcare professionals.

BACKGROUND: In recent years, patient safety has begun to receive particular attention and has become a priority all over the world. Patient Safety Culture (PSC) is widely recognized as a key tenet that must be improved in order to enhance patient safety and prevent adverse events. However, in gynecology and obstetrics, despite the criticality of the environment, few studies have focused on improving PSC in these units. This study aimed at assessing the effectiveness of an educational program to improve PSC among health professionals working in the obstetric unit of a Tunisian university hospital. METHODS: We conducted a quasi-experimental study in the obstetric unit of a university hospital in Sousse (Tunisia). All the obstetric unit's professionals were invited to take part in the study (n = 95). The intervention consisted of an educational intervention with workshops and self-learning documents on patient safety and quality of care. The study instrument was the French validated version of the Hospital Survey on Patient Safety Culture. Normality of the data was checked using Kolmogorov-Smirnov test. The comparison of dimensions' scores before and after the intervention was carried out by the chi2 test. The significance level was set at 0.05. RESULTS: In total, 73 participants gave survey feedback in pre-test and 68 in post-test (response rates of 76.8% and 71.6, respectively). Eight dimensions improved significantly between pre- and post-tests. These dimensions were D2 "Frequency of adverse events reported" (from 30.1 to 65.6%, p < 0.001), D3 "Supervisor/Manager expectations and actions promoting patient safety" (from 38.0 to 76.8%, p < 0.001), D4 "Continuous improvement and organizational learning" (from 37.5 to 41.0%, p < 0.01), D5 "Teamwork within units" (from 58.2 to 79.7%, p < 0.01), D6 "Communication openness" (from 40.6 to 70.6%, p < 0.001), and D7 "Non-punitive response to error" (from 21.1 to 42.7%, p < 0.01), D9 "Management support for patient safety" (from 26.4 to 72.8%, p < 0.001), and D10 "Teamwork across units" (from 31.4 to 76.2%, p < 0.001). CONCLUSIONS: Educational intervention, including workshops and self-learning as pedagogical tools can improve PSC. The sustainability of the improvements made depends on the collaboration of all personnel to create and promote a culture of safety. Staff commitment at all levels remains the cornerstone of any continuous improvement in the area of patient safety.

New Born Screening of Hemoglobinopathies in a Center Tunisian Population.

Sickle cell diseases, ß-thalassemia, and other hemoglobinopathies are common in Africa. Their distribution differs from one region to another. There are higher frequencies in Western and Northern Africa. Their clinical complications presented a real public health problem in each country. For this, early treatment can improve the severity of these diseases. Hemoglobinopathies targeted by screening are associated with SCD, ß, and α thalassemia. Our study aim is to report our experience with newborn screening for hemoglobinopathy in Tunis. The 156 newborn's cord blood was collected at the time of childbirth in the center region (Farhat Hached Hôspital). We opted for hemoglobin exploration to achieve maximum efficiency and effectiveness in screening. After that, all patients suspected to have hemoglobinopathies are affected by molecular investigation. Our findings showed the presence of some hemoglobinopathies such as ß-thalassemia and α-thalassemia with the following frequencies: 12% and 0.33%. The molecular results show the presence of HBB: c.93-21G>A, IVS-I-110G>A, HBBc. -106G>A -56G>C, HBBc.404T>C, Hb Yaounde described for the first time in Tunisia and α 3,7 . In conclusion, newborn screening diagnoses neonates with different examples of hemoglobinopathies, which will be beneficial not only for the care of the child but also for genetic counseling of the potential risk's parents.

Prevalence of antibodies against a cyclic peptide mimicking the FG loop of the human papillomavirus type 16 capsid among Tunisian women.

BACKGROUND: In the past decade, cervical cancer has gone from being the second to the fourth most common cancer in women worldwide, but remains the second most common in developing countries. This cancer is most commonly caused by high-risk types of human papillomavirus (HPV), mainly type 16 (HPV16), which are sexually transmitted. This study aimed to investigate the usefulness of a cyclic synthetic peptide designed from the major L1 capsid protein of HPV16 for detecting anti-HPV16 antibodies. METHODS: We designed and synthetized a peptide that corresponds to the full sequence of the surface-exposed FG loop. We tested the antigenicity of the linear and the cyclic peptides against HPV16 L1 monoclonal antibodies. We used ELISA to detect anti-peptide antibodies in sera and cervical secretions of 179 Tunisian women, and we applied polymerase chain reaction and direct sequencing methods to detect and genotype HPV DNA. RESULTS: Both the linear and the cyclic peptides were recognized by the same neutralizing monoclonal antibodies, but the cyclic peptide was more reactive with human sera. The prevalence of the anti-peptide antibodies in sera was higher in women with low-grade squamous intraepithelial lesions (LGSIL) than in women with high-grade squamous intraepithelial lesions (HGSIL) (44% and 15%, respectively). This contrasts with HPV16 DNA prevalence. Compared to women from the general population, systemic IgG prevalence was significantly higher among sex workers (25%; P = 0.002) and women with LGSIL (44%; P = 0.001). In addition, systemic IgA and cervical IgG prevalence was higher among sex workers only (P = 0.002 and P = 0.001, respectively). We did not observe anti-peptide IgG antibodies in women with a current HPV16 infection. CONCLUSION: Anti-peptide IgG in sera or in cervical secretions could be markers of an effective natural immunization against HPV16. This may open novel perspectives for monitoring vaccinated women and for the design of synthetic peptide-based vaccines.

Small supernumerary marker chromosomes (sSMC) and male infertility: characterization of five new cases, review of the literature, and perspectives.

PURPOSE: To characterize small supernumerary marker chromosomes (sSMC) in infertile males RESEARCH QUESTION: Are molecular cytogenetic methods still relevant for the identification and characterization of sSMC in the era of next-generation sequencing? METHODS: In this paper, we report five males with oligoasthenozoospermia or azoospermia with a history of recurrent pregnancy loss in partnership in four cases. R-banding karyotyping and fluorescence in situ hybridization (FISH) analysis were performed and showed sSMC in all five cases. Microdissection and reverse-FISH were performed in one case. RESULTS: One sSMC, each, was derived from chromosome 15 and an X-chromosome; two sSMC were derivatives of chromosome 22. The fifth sSMC was a ring chromosome 4 complemented by a deletion of the same region 4p14 to 4p16.1 in one of the normal chromosomes 4. All markers were mosaics except one of sSMC(22). CONCLUSION: Through this study, we emphasize the necessity of a proper combination of high-throughput techniques with conventional cytogenetic and FISH methods. This could provide a personalized diagnostic and accurate results for the patients suffering from infertility or RPL. We also highlight FISH analyses, which are essential tools for detecting sSMC in infertile patients. In fact, despite its entire composition of heterochromatin, sSMC can have effects on spermatogenesis by producing mechanical perturbations during meiosis and increasing meiotic nondisjunction rate. This would contribute to understand the exact chromosomal mechanism disrupting the natural and the assisted reproduction leading to offer a personalized support.

Subtelomeric Rearrangements in Patients with Recurrent Miscarriage.

BACHGROUND: The subtelomeric rearrangements are increasingly being investigated in cases of idiopathic intellectual disabilities (ID) and congenital abnormalities (CA) but are also thought to be responsible for unexplained recurrent miscarriage (RM). Such rearrangements can go unnoticed through conventional cytogenetic techniques and are undetectable even with high-resolution molecular cytogenetic techniques such as array comparative genomic hybridization (aCGH), especially when DNA of the stillbirth or families are not available. The aim of the study is to evaluate the rate of subtelomeric rearrangements in patients with RM. MATERIALS AND METHODS: In this cross-sectional study, fluorescent in situ hybridization (FISH), based on ToTelVysion telomeric probes, was undertaken for 21 clinically normal couples exhibiting a "normal" karyotype with at least two abortions. Approximately 62% had RM with a history of stillbirth or CA/ID while the other 38% had only RM. RESULTS: FISH detected one cryptic rearrangement between chromosomes 3q and 4p in the female partner of a couple (III:4) [46,XX,ish t(3;4)(q28-,p16+;p16-,q28+)(D3S4559+,D3S4560-,D4S3359+; D3S4560+, D4S3359- ,D4S2930+)] who presented a history of RM and family history of ID and CA. Analysis of the other family members of the woman showed that her sisters (III:6 and III:11) and brother (III:8) were also carriers of the same subtelomeric translocation t(3;4)(q28;p16). CONCLUSION: We conclude that subtelomeric FISH should be undertaken in couples with RM especially those who not only have abortions but also have had at least one child with ID and/or CA, or other clinically recognizable syndromes. For balanced and cryptic anomalies, subtelomeric FISH still remains the most suitable and effective tool in characterising such chromosomal rearrangements in RM couples.

Multiplex Minisequencing of the HBB Gene: A Rapid Strategy to Confirm the Most Frequent ß-Thalassemia Mutations in the Tunisian Population.

The ß hemoglobinopathies [ß-thalassemia (ß-thal) and structural hemoglobin (Hb) variants such as Hb S (HBB: c.20A > T) and Hb E (HBB: c.79G > A)] are among the most common inherited diseases worldwide. In Tunisia, due to the high prevalence of consanguineous marriages, the recurrent risk of this disease is high. The average prevalence of hemoglobinopathies is 4.48%, reaching 12.50% in some focus regions. The molecular investigations on thalassemia contributed to establishing the spectrum of mutations in the Tunisian population. The total number of HBB gene mutations identified was 24. The two most frequent mutations, codon 39 (C > T) (HBB: c.118C > T) and IVS-I-110 (G > A) (HBB: c.93-21G > A) accounted for 70.0% of the total encountered ß-thal cases. These two mutations together with IVS-I-2 (T > G) (HBB: c.92 + 2T > G) and the Hb S variant account for more than 90.0% of all HBB genetic variants in Tunisia. Thus, developing rapid, inexpensive and reliable mutation-specific molecular diagnostic assays targeting our Tunisian populations is our aim to facilitate routine detection of hemoglobinopathies. In this report, we describe the successful application of the multiplex minisequencing assay as an alternative strategy for genetic diagnosis of HBB gene disorders in Tunisia.

Calreticulin expression in infiltrating ductal breast carcinomas: relationships with disease progression and humoral immune responses.

The aim of this study was to evaluate calreticulin expression in infiltrating ductal breast carcinomas (IDCAs), as well as its relationships with clinicopathological parameters of the disease. Using a two-dimensional gel electrophoresis/matrix-assisted laser desorption ionization time of flight mass spectrometry investigation coupled to an immunohistochemical approach, we have assessed the expression of calreticulin in IDCAs, as well as in other types of breast tumors. The humoral immune response against calreticulin was estimated using a serological proteomics-based strategy. Proteomic analyses revealed an increased expression of calreticulin in IDCA tumors. Using immunohistochemistry, overexpression of calreticulin was confirmed in 51 additional tumor specimens. Statistical analyses revealed, however, no significant correlations between calreticulin expression and clinicopathological parameters of the disease including tumor stage, patient age, SBR grade, and lymph node metastasis occurrence. A significant association was found, however, with estrogen receptor status. This study demonstrates the upregulation of calreticulin in IDCA tissues which may highlight its involvement in breast cancer development. Our findings also support a link between calreticulin expression and estrogen transduction pathways. Our results do not, however, support the involvement of calreticulin in the development of a humoral immune response in IDCAs.

[Towards a better knowledge of breast cancer physiopathology: the proteomics approach]. / Pour une meilleure compréhension de la physiopathologie des cancers mammaires : l'approche protéomique.

Breast cancer represents a major public health problem. Approximately one woman in ten is likely to develop a malignant tumor of the breast in their lifetime. The frequency of breast cancer is rising steadily for 20 years and the practical benefits in the diagnosis, prognosis and treatment of this disease are still too limited. Actually, there is no tumor marker with a specificity and sensitivity sufficient to have an utility in clinical and early diagnosis of breast cancer, although, carcinoembryonic antigen (CEA), MUC-1 and CA 15-3 were reported to be useful as markers for monitoring this disease. Thus, proteomics approaches are needed for the discovery and the identification of new protein biomarkers that may allow a better understanding of biological mechanisms of breast tumor development and serve as potential therapeutic targets. This article reviews advances in this field, as well as, the major contribution of these markers in breast pathology, with a focus on their biological characteristics and their clinical and therapeutic involvement.

Expression of the molecular chaperone αB-crystallin in infiltrating ductal breast carcinomas and the significance thereof: an immunohistochemical and proteomics-based strategy.

This study aims to evaluate αB-crystallin expression in infiltrating ductal breast carcinomas (IDCAs), as well as, its prognostic significance. Using a two-dimensional electrophoresis matrix-assisted laser desorption/ionisation-time of flight mass spectrometry investigation coupled to an immunohistochemical approach, we have assessed the expression of αB-crystallin in IDCAs, as well as, in other types of breast tumors (invasive lobular carcinomas, medullary carcinomas, and in situ ductal carcinomas). Correlation between αB-crystallin expression and clinicopathological parameters of breast cancer has also been investigated. Proteomic analyses revealed an increased expression of αB-crystallin in IDCA tumors compared to adjacent nontumor tissues. Overexpression of this molecular chaperone was further confirmed in 51 tumor specimens. Statistical analyses revealed, however, no significant correlations between αB-crystallin expression and clinicopathological parameters of the disease (tumor stage, patient age, hormone receptors, SBR grade, and lymph node metastases). This study demonstrates the upregulation of αB-crystallin in IDCA tissues which may highlight its possible involvement in breast cancer development. Our findings do not, however, support the involvement of this molecular chaperone in the progression of this disease.

Assessment of the clinical significance of antigenic and functional levels of α1-proteinase inhibitor (α1-Pi) in infiltrating ductal breast carcinomas.

OBJECTIVES: To determine the clinical significance of α1-proteinase inhibitor (α1-Pi) in infiltrating ductal breast carcinoma patients. DESIGN AND METHODS: Serum levels of α1-Pi, tryptic specific inhibitory capacity and α1-Pi circulating immune complexes were determined using radial immunodiffusion, BAPNA assays and ELISA, respectively. 2-DE-MS and immunohistochemistry were performed to examine α1-Pi protein expression. RESULTS: A decreased serum level of α1-Pi was found among breast cancer patients in comparison to controls. In addition, we found a significantly decreased mean level of α1-Pi in the node metastatic group when compared to node negative patients. However, the functional activity of the inhibitor did not decrease proportionately. Through 2-DE analyses, a differential expression of α1-Pi isoforms according to tumor stage and node metastatic development was found. CONCLUSIONS: Both α1-Pi levels and specific activity could be a source of complementary clinical information and may provide useful information for a better understanding of the mechanisms of metastasis.

An elongation factor-like protein (EF-Tu) elicits a humoral response in infiltrating ductal breast carcinomas: an immunoproteomics investigation.

OBJECTIVES: In the current study, we have used an immunoproteomics approach to identify proteins that commonly elicit a humoral response in patients with infiltrating ductal carcinomas of the breast. DESIGN AND METHODS: Sera obtained at the time of diagnosis from 40 patients with invasive breast cancer and 42 healthy controls were screened for the presence of IgG antibodies to MCF-7 cell line proteins using a serological proteomics-based approach. RESULTS: An immunoreactive protein detected in sera from 21 of 40 patients was isolated and subsequently identified as elongation factor-Tu. CONCLUSIONS: The immunoproteomic approach implemented here offers a powerful tool for determining novel tumor antigens that induce a humoral immune response in cancer patients. From our findings, the immunoreactive EF-Tu protein and/or the related circulating antibodies may display clinical usefulness as potential diagnostic markers and provide a means for a better understanding of the molecular mechanisms underlying breast cancer development.

Sublingual misoprostol for first trimester termination of pregnancy.

OBJECTIVES: To compare blood loss, efficiency, and acceptability of repeated doses of sublingual misoprostol with the standard Tunisian regimen of mifepristone-misoprostol for first trimester medical abortion. METHODS: A prospective randomized trial of 252 healthy pregnant women requesting medical abortion in the first trimester (up to 56 days). Participants were randomized to receive 200mg of oral mifepristone followed by 400 microg of oral misoprostol (group 1) or 800 microg of sublingual misoprostol repeated every 4 hours for up to a maximum of 3 doses (group 2). Primary outcome was blood loss assessed by decrease in hematocrit. RESULTS: Mean decrease in hematocrit at follow-up was significantly greater in group 1 than in group 2 (3.65%+/-1.18% vs 2.69%+/-1.89%, respectively; P=0.02). There was no difference in efficiency rates between groups 1 and 2 (94.5% vs 92.1%; P=0.7). Comparable proportions of women experiencing at least one adverse effect after misoprostol administration were reported in groups 1 and 2 (81.7% vs 79.4%; P=0.75). CONCLUSION: Compared with the most widely used regimen in Tunisia (mifepristone-misoprostol), sublingual misoprostol alone induces less blood loss (although not clinically significant); it is less expensive and offers reduced interval time to expulsion.

Proteomics-based identification of alpha1-antitrypsin and haptoglobin precursors as novel serum markers in infiltrating ductal breast carcinomas.

BACKGROUND: The identification of pathological markers of breast cancer for either diagnosis, treatment response or for survival is of critical importance. METHODS: Serum protein profiling using 2-DE separations coupled to matrix-assisted laser desorption ionization mass spectrometry has been used to explore protein alterations in patients with infiltrating ductal breast carcinomas (IDCA). Sera from 39 breast cancer patients and 40 healthy controls were selected for screening study using 2-DE combined with MS. The protein expression patterns obtained after the depletion of high abundance proteins was determined by coomassie blue G-250 stain after 2-DE electrophoresis. RESULTS: Six proteins that expressed differentially in the IDCA group were found. The expression levels of four isoforms corresponding to haptoglobin precursor and two isoforms of alpha1-antitrypsin precursor (alpha1-AT) were upregulated in sera from breast cancer patients. There was an increased expression of both proteins in the sera of patients with various tumor stages (I, II, III) in comparison to healthy women. Applying immunohistochemistry, we further validated alpha1-AT immunoreactivity in 51 formalin-fixed paraffin-embedded sections of breast tumors. Enhanced expression of alpha1-AT like activity has been found in IDCA breast tumors, as well as, in different histological types of breast cancer. No significant association has been found with lymph node occurrence, while in high tumor categories a tendency to an increased expression of alpha1-AT has been found, thereby suggesting a possible role of this protein in tumor growth. CONCLUSIONS: These proteins may constitute new and useful markers of breast cancer that offer a clue to a better understanding of inflammatory pathways and carcinogenesis events linked to breast cancer progression.

Asymptomatic horn rudimentary pregnant uterine rupture with a viable fetus.

BACKGROUND: Rupture of pregnant rudimentary horn in a pseudounicornuate uterus is usually resulting in severe and dramatic haemoperitoneum at the beginning of the second trimester of gestation. Advanced abdominal pregnancy due to horn rudimentary uterine rupture with delivery of a viable fetus is exceptional. AIM: To analyse obstetrical entailments, diagnosis and current concepts of management of advanced abdominal pregnancy secondary to rudimentary horn rupture. CASE: An asymptomatic ruptured rudimentary horn pregnancy in a 31-year-old, second gravida, is reported. She was referred to our maternity for anhidramnios at estimated gestational age of 30 weeks. An advanced abdominal pregnancy was diagnosed with sonographic features suggestive of horn rudimentary uterine rupture. Elective laparotomy was performed and a healthy infant was delivered. Excision of the rudimentary horn was done and an uneventful recovery followed. CONCLUSION: An unusual sonographic appearance of the placenta with anhidramnios must first lead to consider the diagnosis of advanced abdominal pregnancy in time to save the surgeon from an unpleasant and dangerous surprise and to increase the chance of materno-fetal survival.

Identification of tumor antigens that elicit a humoral immune response in breast cancer patients' sera by serological proteome analysis (SERPA).

BACKGROUND: In this study we applied a serological proteomics-based approach (SERPA) to identify tumor antigens that commonly induce a humoral immune response in patients with infiltrating ductal breast carcinomas. METHODS: Sera obtained at the time of diagnosis from 40 patients with invasive breast cancer and 42 healthy controls were screened individually for the presence of IgG antibodies to MCF-7 cell line proteins. Immunoreactive proteins were isolated and subsequently identified by MALDI-TOF mass spectrometry. RESULTS: We identified 26 proteins that reacted with antibodies in the sera from breast cancer patients. Among these antigens, a significantly higher frequency occurs against the molecular chaperone HSP60, the tumor suppressor prohibitin, beta-tubulin, the haptoglobin-related protein and peroxiredoxin-2. Immunoreactivity to hnRNPK, Mn-SOD and F1-ATPase was also clearly detected in the patients group, whereas scarcely in control sera. By contrast, two other antigens identified as cytokeratins 8 and 18, as well as, F1-actin were found to elicit humoral immune responses in both control and breast cancer patients' sera. CONCLUSIONS: The immunoproteomic approach implemented here offers a powerful tool for determining novel tumor antigens that elicit a humoral immune response in patients with invasive breast cancer. These antigens and/or their related circulating antibodies may display clinical usefulness as potential diagnostic markers and provide a means for a better understanding of the molecular mechanisms underlying breast cancer development.

Randomized controlled trial of vaginal misoprostol versus vaginal misoprostol and isosorbide dinitrate for termination of pregnancy at 13-29 weeks.

When compared to the use of 12 hourly 200 microg vaginal misoprostol on its own, the addition of a single dose of 5 mg did not significantly increase the abortion or delivery rate in pregnancy termination at 13-29 weeks gestation. All patients were given intravenous syntocinon at 30 mU/min from the first dose of misoprostol onwards.

[Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study]. / Apport de la corticothérapie anténatale dans la prévention de la maladie des membranes hyalines chez le prematuré. Etude prospective randomisée.

OBJECTIVE: The aim of the study was to determine the feasibility, the cost and the effects of antenatal maternal corticosteroid treatment on preventing respiratory distress syndrome in premature neonates of our population. SUBJECTS AND METHODS: Between January, 1, 1998 and June, 31, 1999, 118 pregnant women at 26-34 weeks' gestation and at a high risk of premature delivery, were prospectively randomized in 2 groups: group 1 received intramusculary 24 mg of betamethasone (12 mg every 24 hours), group 2 didn't receive antenatal corticosteroids. At birth, premature neonates were systematically examined by a neonatologist. RESULTS: 131 premature neonates were born (63 from group 1, 68 from group 2). The incidence and the degree of severity of respiratory distress syndrome, appeared substancially reduced (4.8% vs 27.9%) by the use of antenatal corticosteroids. Moreover, neonatal mortality due to respiratory distress syndrome was statistically less in group 1 than in group 2 (22.9% vs 57%). There was no significant difference in the occurrence of maternal or neonatal corticosteroid complications such as infection between treated group and control subjects. We estimated a potential annual savings of 21 thousands tunisian dinars, when the cost implications for antenatal corticosteroid therapy were estimated to 2 thousands tunisian dinars. CONCLUSION: Maternal administration of corticosteroids before preterm delivery results in a decrease in the incidence and severity of respiratory distress syndrome and a decrease in neonatal mortality rate among premature neonates born to treated versus untreated mothers at 26-34 weeks' gestation; added to an annual savings estimated to 21 thousands tunisian dinars.