[Epidemiology of postpartum hemorrhages in the Umbrian population in the years 2006-2017.] / Epidemiologia delle emorragie post partum nella popolazione umbra nel periodo 2006-2017.

INTRODUCTION: Postpartum haemorrhage (PPH) is one of the main causes of mortality and severe maternal morbidity and its incidence is increasing also in Western countries. Aim of this study is to estimate the incidence and the trend of PPH in the Umbrian population using the validated Umbrian health database and to identify possible determinants for the development of PPH. METHODS: The source of the data was the regional Healthcare Database of the Umbria Region. The population of interest was represented by women who gave birth in Umbria between 2006 and 2017. The PPH was identified from the hospital data using the ICD-9-CM 666.x codes. Demographic data, principal and secondary diagnoses and data on maternal morbidity and blood component transfusion were collected. The incidence of PPH was calculated taking into account cases of PPH over the total number of births. The determinants of PPH, the associated morbidity and the variation in the severity of the PPH over time have been identified by logistic regression models. RESULTS: In Umbria, between 2006 and 2017, 93,403 births were registered (69% by vaginal delivery and 31% by caesarean section) and the rate of caesarean sections decreased by about 4%. The incidence of PPH increased three-fold during this period with an increase (p<0.001) of women with PPH who received transfusions. Regarding the caesarean sections, the PPH trend increased by 53% (p=0.3), while in the vaginal deliveries the PPHs increased by 233% (p<0.001). Logistic regression analysis showed that possible risk factors for the occurrence of PPH are maternal morbidity (OR 22.8, 95% CI 18.5-30.0), twin birth (OR 2.0, 95% CI 1.3-3.2) and antepartum haemorrhage (OR 5.7, 95% CI 3.1-10.4). CONCLUSIONS: The incidence of PPH has increased in recent years, while the morbidity associated with PPH has remained substantially unchanged. The study identified several risk factors responsible for PPH that can be used in the monitoring of pregnant women and for planning prevention strategies such as Patient Blood Management.

[Postpartum haemorrhage in Umbria: accuracy of the regional health information system for the code ICD-9-CM 666.x.] / Emorragia post partum in Umbria: accuratezza del sistema informativo sanitario regionale per il codice ICD-9-CM 666.x.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of morbidity and mortality for pregnant women. Administrative databases are useful sources of information for the assessment of PPH and related outcomes, once the corresponding ICD-9-CM code is validated. The objective of the present study is to evaluate the accuracy of the ICD-9-CM code related to PPH. MATERIAL AND METHODS: Source of the data was the Regional Healthcare Database of the Umbria Region. The population of interest were women with at least 20 weeks of gestation that delivered in any hospital in the Umbria Region during 2012-2016. Cases of interest were identified using the ICD-9-CM 666.x code. For validation purposes, both cases (women who delivered and developed PPH) and non-cases (women who delivered without occurrence of PPH) were considered and algorithms proposed. The basic criterion used for the validity of ICD-9-CM codes was the presence of bleeding ≥500 ml. Additional criteria based on values of haemoglobin or transfusion of red blood cells were considered. Sensitivity, specificity and predictive values were calculated. RESULTS: Medical charts of 422 cases and 200 non-cases were examined. Accuracy results for code 666.x related to the presence of bleeding ≥500 ml were: sensitivity 97% (95% CI, 96-99%), specificity 70% (65-76%), positive predictive value (PPV) 79% (76-82%) and negative predictive value (NPV) 95% (91-97%). The best algorithm was the one that, in addition to the basic criterion, considered both the haemoglobin values and red blood cell transfusion: sensitivity 93% (90-95%), specificity 85% (80-90%), PPV 92% (89-94%) and NPV 86% (81-90%). ICD-9 subcodes showed a higher specificity and PPV for immediate bleeding (666.0, 666.1) than delayed or secondary haemorrhage (666.2). CONCLUSIONS: The accuracy data from the present study confirm that the Regional Healthcare Database of the Umbria Region can be used as a reliable source for the evaluation of epidemiological studies relating to PPHs, in order to improve the quality of maternity care.

Oral iron-based interventions for prevention of critical outcomes in pregnancy and postnatal care: An overview and update of systematic reviews.

OBJECTIVE: The aim of this work was to summarize and update the evidence concerning oral iron-based interventions compared to placebo or no iron-based interventions to prevent critical outcomes in pregnancy or treat critical outcomes in the postpartum phase. METHOD: Published systematic reviews (Feb 2018) and primary studies (from 2015 to March 2018) retrieved from MEDLINE, EMBASE, and the Cochrane Library were examined. The AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool was used to assess the quality of reviews. GRADE was used to rate the quality of the evidence for critical outcomes. RESULTS: Antenatal care: Compared to placebo/no treatment, iron-based therapies reduced maternal anemia at term by 59% (seven trials at low risk of bias, RR 0.41, 95% CI 0.23-0.73; I2  = 86%; moderate-quality evidence) and maternal iron deficiency anemia by 67% (RR 0.33, 95% CI 0.16-0.69; I2  = 49%). There was no evidence of difference between iron-based therapies vs control in terms of side effects (RR 1.42, 95% CI 0.91-2.21), preterm delivery (13 studies: RR 0.93, 95% CI 0.84-1.03; low-quality evidence), low birthweight (RR 0.94, 95% CI 0.79-1.13; low-quality evidence) and infant mortality (RR 0.93, 0.72-1.20; low-quality evidence). POSTNATAL CARE: There was insufficient evidence to determine whether iron-based therapies can reduce postpartum anemia. CONCLUSION: Iron supplementation is effective in preventing maternal anemia at term but not low birthweight, preterm delivery or infant mortality.

Diagnostic, preventive and therapeutic evidence in obstetrics for the implementation of patient blood management: a systematic review protocol.

INTRODUCTION: Patientblood management (PBM) is defined as the application of evidence-based diagnostic, preventive and therapeutic approaches designed to maintain haemoglobin concentration, optimise haemostasis and minimise blood loss in an effort to improve patient outcome. We propose a protocol for the assessment of the evidence of diagnostic, preventive and therapeutic approaches for the management of relevant outcomes in obstetrics with the aim to create a framework for PBM implementation. METHODS AND ANALYSIS: Diagnostic, preventive and therapeutic tools will be considered in the gynaecological conditions and obstetrics setting (antenatal care, peripartum care and maternity care). For each condition, (1) clinical questions based on prioritised outcomes will be developed; (2) evidence will be retrieved systematically from electronic medical literature (MEDLINE, EMBASE, the Cochrane Library, Web of Science, and CINAHL); (3) quality of the reviews will be assessed using the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist; quality of primary intervention studies will be assessed using the risk of bias tool (Cochrane method); quality of diagnostic primary studies will be assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies); (4) the Grading of Recommendations Assessment, Development and Evaluation method will be applied to rate the quality of the evidence and to develop recommendations. ETHICS AND DISSEMINATION: For each diagnostic, preventive or therapeutic intervention evaluated, a manuscript comprising the evidence retrieved and the recommendation produced will be provided and published in peer-reviewed journals. Ethical approval is not required.

A systematic review found that deviations from intention-to-treat are common in randomized trials and systematic reviews.

OBJECTIVES: To describe the characteristics, and estimate the incidence, of trials included in systematic reviews deviating from the intention-to-treat (ITT) principle. STUDY DESIGN AND SETTING: A 5% random sample of reviews were selected (Medline 2006-2010). Trials from reviews were classified based on the ITT: (1) ITT trials (trials reporting standard ITT analyses); (2) modified ITT (mITT) trials (modified ITT; trials deviating from standard ITT); or (3) no ITT trials. RESULTS: Of 222 reviews, 81 (36%) included at least one mITT trial. Reviews with mITT trials were more likely to contain trials that used placebo, that investigated drugs, and that reported favorable results. The incidence of reviews with mITT trial ranged from 29% (17/58) to 48% (23/48). Of the 2,349 trials, 597 (25.4%) were classified as ITT trials, 323 (13.8%) as mITT trials, and 1,429 (60.8%) as no ITT trials. The mITT trials were more likely to have reported exclusions compared to studies classified as ITT trials and to have received funding. CONCLUSION: The reporting of the type of ITT may differ according to the clinical area and the type of intervention. Deviation from ITT in randomized controlled trials is a widespread phenomenon that significantly affects systematic reviews.

The Molecular Spectrum of ß- and α-Thalassemia Mutations in Non-Endemic Umbria, Central Italy.

The aim of this study was to describe the mutational spectrum of hemoglobinopathies during the period 1988-2015 in Umbria, Central Italy, which has never been considered endemic for these conditions. Twenty-four different ß-globin gene mutations were identified in 188 patients and eight different α-globin gene mutations in 74 patients. Sixty percent ß-thalassemia (ß-thal), 85.0% sickle cell disease, 44.0% Hb S (HBB: c.20A>T)/ß-thal and 85.0% compound heterozygotes for hemoglobin (Hb) variant-carrying patients were diagnosed or molecularly characterized in the last 3 years. Moreover, most homozygous or compound heterozygous patients (84.5%) came from foreign countries, while only 15.5% were of Italian origin. These data are in accordance with the increasing foreign resident population in Umbria, which has nearly doubled in 10 years (2004-2014). Different from ß-globin gene variations, no increasing trend in α defects was observed in our study cohort. Consistently, 58.0% of patients have an Italian origin, suggesting no broad influence of foreign migration in the α-globin genes genetic background. As few defects are prevalent in each country of origin or ethnic group, their knowledge may provide a proper strategy for the identification of mutations in immigrant individuals in a non-endemic region and be important for carrier identification and prenatal screening.

Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study.

OBJECTIVE: To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials. DESIGN: Meta-epidemiological study. DATA SOURCES: Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 310 randomised trials were included. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: From each year searched, random selection of 5% of intervention reviews with a meta-analysis that included at least one trial that deviated from the standard intention to treat approach. Basic characteristics of the systematic reviews and randomised trials were extracted. Information on the reporting of intention to treat analysis, outcome data, risk of bias items, post-randomisation exclusions, and funding were extracted from each trial. Trials were classified as: ITT (reporting the standard intention to treat approach), mITT (reporting a deviation from the standard approach), and no ITT (reporting no approach). Within each meta-analysis, treatment effects were compared between mITT and ITT trials, and between mITT and no ITT trials. The ratio of odds ratios was calculated (value <1 indicated larger treatment effects in mITT trials than in other trial categories). RESULTS: 50 meta-analyses and 322 comparisons of randomised trials (from 84 ITT trials, 118 mITT trials, and 108 no ITT trials; 12 trials contributed twice to the analysis) were examined. Compared with ITT trials, mITT trials showed a larger intervention effect (pooled ratio of odds ratios 0.83 (95% confidence interval 0.71 to 0.96), P=0.01; between meta-analyses variance τ(2)=0.13). Adjustments for sample size, type of centre, funding, items of risk of bias, post-randomisation exclusions, and variance of log odds ratio yielded consistent results (0.80 (0.69 to 0.94), P=0.005; τ(2)=0.08). After exclusion of five influential studies, results remained consistent (0.85 (0.75 to 0.98); τ(2)=0.08). The comparison between mITT trials and no ITT trials showed no statistical difference between the two groups (adjusted ratio of odds ratios 0.92 (0.70 to 1.23); τ(2)=0.57). CONCLUSIONS: Trials that deviated from the intention to treat analysis showed larger intervention effects than trials that reported the standard approach. Where an intention to treat analysis is impossible to perform, authors should clearly report who is included in the analysis and attempt to perform multiple imputations.

Audit of the clinical use of fresh-frozen plasma in Umbria: study design and results of the pilot phase.

BACKGROUND: Fresh-frozen plasma (FFP) is unanimously recognised by international guidelines as the blood component of choice for the management of acute haemorrhage when accompanied by disorders of haemostasis, for disseminated intravascular coagulation in the presence of haemorrhage, for rare bleeding disorders when specific clotting factor concentrates are not available and for thrombotic thrombocytopenic purpura. The literature, however, reports a high percentage of inappropriate requests for FFP. This article presents the results of a pilot study of clinical auditing of the use of FFP in the Region of Umbria (Italy). METHODS: This study was based on the examination of the requests for FFP made in April 2006 to four Immunotransfusion Services (ITS) in Umbria and of the clinical records of the patients receiving transfusions. The following indicators were identified and evaluated: completeness of the request, appropriateness of the indication and the dose, completeness of the records in the clinical charts, adverse events, in-hospital morbidity and mortality, efficacy of the treatment (evaluated by analysing the changes between pre- and post-transfusion coagulation test results) and, as an indicator of the process, the correspondence between data in the paper request form and in the computerised database. The data were extracted from the ITS databases, from the paper request forms and from the patients' clinical records. RESULTS: Two hundred and twenty-one requests (615 units of FFP) for 109 patients and 92.8% of the related clinical records were examined. The patients were admitted in medical (22.9%), surgical (51.4%) and critical care units (25.7%). In 50.7% of the cases, the completeness of the data in the individual requests was good (65-80% of the fields filled in). The indication was appropriate in 31.5% of the requests evaluated (56.1% of the total), with no difference related to different requesters. The dosage was appropriate in 62.7% of the requests evaluated (62% of the total). A comparison of pre- and posttransfusion laboratory data showed a significant correction of pathological values (p=0.02) only for the International Normalised Ratio (INR). CONCLUSIONS: Critical areas that should be targeted by interventions to improve plasma usage are those related to the appropriateness of the indication, the completeness of the data entered in the request forms and the data recorded in the clinical charts.

The good use of plasma. A critical analysis of five international guidelines.

BACKGROUND: The clinical use of fresh-frozen plasma (FFP) is progressively increasing both nationally and internationally, despite the fact that many studies have shown the weaknesses of the indications for its use. Guidelines on the good use of plasma have, therefore, been adopted in various countries. The aim of the present study was to analyse some of the existing guidelines on the good use of plasma, applying a scientifically validated method, as a preliminary step in the implementation of Regional guidelines. METHODS: Abibliographic search (1990-2006) was conducted in databases, websites, and the archives of scientific societies. Relevant articles were recovered in full. The selected guidelines were evaluated using theAGREE instrument, which assesses the completeness and structural quality of the guidelines and, in some aspects, the contents of the recommendations. The project, co-ordinated by the Regional Centre for Co-ordination and Compensation (CRCC) and carried out by four Services of Immunohaematology and Transfusion (SIT) in Umbria, was funded by the Region of Umbria and approved by the four health care institutions involved. RESULTS: The bibliographic search yielded 3067 abstracts of which 239 were considered relevant. The analysis of these led to the recovery of 11 guidelines, among which five were selected: those from the British Committee for Standards in Haematology, theAgence Française de Securité Sanitaire de Produits de Sante, the Canadian Members of the Expert Working Group, the American Society of Anesthesiologists Task Force on Blood Component Therapy and the National Health and Medical Research Council (NHMRC)/Australasian Society of Blood Transfusion. CONCLUSIONS: None of the guidelines analysed obtained a score higher than 50% in all the domains of the AGREE score. There was no evidence of a tendency to improvement over time in the guidelines analysed. Objective evaluation of the guidelines analysed could provide the starting point for the subsequent production of similar documents.