Language outcomes at 36 months in prematurely born children is associated with the quality of developmental care in NICUs.

OBJECTIVE: The aim of this study was to examine the relationship between the quality levels of NICU developmental care (DC) and language skills at 36 months in very preterm (VPT) children. STUDY DESIGN: Language skills of 78 VPT children from 19 NICUs and 90 full-term controls was assessed using a standardized language test. We compared children' language task performance by splitting NICUs into units with high- and low-quality of DC according to two main factors: (1) infant centered care (ICC), and (2) infant pain management (IPM). RESULTS: VPT children from low-care units with respect to ICC obtained lower scores in sentence comprehension, compared to children from high-care units. No differences were found between preterm children from high-quality ICC NICUs and full-term children. CONCLUSIONS: Findings suggest that higher quality of DC related to infant centered care can mitigate delays in language skills at 36 months in children born VPT.

Neonatal developmental care in infant pain management and internalizing behaviours at 18 months in prematurely born children.

BACKGROUND: Very preterm infants are exposed to adverse stressful experiences, which may result in long-term behavioural outcomes. The developmental care practices, including pain management and environmental support, can minimize the effects of stress exposure. However, developmental care quality levels may vary among Neonatal Intensive Care Units (NICUs) and little is known about how differences in developmental care quality affect long-term behavioural outcomes. The aim of this study was to examine the relation between quality levels NICUs developmental care and behaviour problems at 18 months corrected age in preterm children. METHODS: The behaviour of 134 preterm children from 22 NICUs and 123 full-term controls was examined using the questionnaire Child Behaviour Checklist 1½-5. We compared the behavioural profile of children by splitting NICUs into units with high- and low quality of developmental care according to two main care factors: (1) infant centered care (ICC) index, and (2) infant pain management (IPM) index. RESULTS: Preterm children from low-care units in IPM group reported higher scores in Internalizing Problems, compared to children from high-care units. No differences were found between preterm children from high-care in IPM and full-term children. No significant IPM effect was found for externalizing problems. No significant ICC effect emerged both for internalizing and externalizing problems. CONCLUSIONS: Findings suggest that higher quality of developmental care related to infant pain management can mitigate behavioural problems at 18 months in children born preterm, to such an extent that preterm children exhibit a behavioural profile similar to that displayed by full-term children.

Neonatology and the caesarean section.

The origins of the use of the Caesarean section date far back in human history. Traces of this procedure can be found in Greek mythology and in the history of Ancient Rome. Many documents about the history of religion make reference to a delivery from the abdomen.

Systematic quality control for management of ST elevation acute myocardial infarction in setting of local network.

AIM: Adherence to evidence based guidelines, assessed by measuring key indicators, allows to detect, evaluate and improve quality of care. Since 2004 in Carlo Poma Hospital, following the introduction of a network for ST-elevation myocardial infarction (STEMI) management, the authors carried out a clinical database in order to measure quality of care in STEMI patients. MATERIALS AND METHODS: A real time upgradable database was developed, to assess clinical practice in myocardial infarction management. The authors evaluated prevalence and control of risk factors, pharmacological therapies and interventional procedures, pathways and delays to care. RESULTS: From 1 February 2004 to 31 January 2008, 1,714 consecutive patients with myocardial infarction were admitted in the Intensive Care Unit (ICU). Primary percutaneous coronary intervention (PCI) was performed in 85% of STEMI patients. Door to balloon time was greater than 90 min in only 17% of patients, of whom 88% coming from emergency department and 12% transferred by 118. CONCLUSION: In the authors' experience quality indicators proved useful in the management of myocardial infarction. Implementation of 118 and improvement of pre-hospital diagnosis in setting of local network can reduce time to treatment.

Opioids for neonates receiving mechanical ventilation: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of opioid analgesics, compared to placebo, no drug, or other non-opioid analgesics or sedatives, on pain, duration of mechanical ventilation, mortality, growth and neurodevelopmental outcomes in newborn infants on mechanical ventilation. METHODS: This was a systematic review and meta-analysis of randomised controlled trials (RCTs). Data sources used were Cochrane, MEDLINE, EMBASE and CINAHL databases, and references from review articles. RCTs or quasi-RCTs comparing opioids to a control, or to other analgesics or sedatives in newborn infants on mechanical ventilation were reviewed. RESULTS: A total of 13 studies on 1505 infants were included. Infants given opioids showed reduced Premature Infant Pain Profile (PIPP) scores compared to the control group (weighted mean difference (WMD) -1.71, 95% CI -3.18 to -0.24). Heterogeneity was significantly high in all analyses of pain. Meta-analyses of mortality, duration of mechanical ventilation and long-term and short-term neurodevelopmental outcomes showed no statistically significant differences. Very preterm infants given morphine took significantly longer to reach full enteral feeding than those in control groups (WMD 2.10 days, 95% CI 0.35 to 3.85). One study that compared morphine with midazolam showed similar pain scores, but fewer adverse effects with morphine. CONCLUSIONS: There is insufficient evidence to recommend routine use of opioids in mechanically ventilated newborns. Opioids should be used selectively, when indicated by clinical judgment and evaluation of pain indicators. If sedation is required, morphine is safer than midazolam.

[Mortality triplicates in acute myocardial infarction patients affected by chronic renal failure]. / L'insufficienza renale triplica il rischio di morte intraospedaliera nell'Infarto del Miocardio.

In order to calculate the cardiovascular risk in patients with chronic renal failure (CRF), we retrospectively analyzed 1482 acute myocardial infarctions (AMIs) treated in the ICU at C. Poma General Hospital, Mantua, Italy, from 1 December 2004 to 31 July 2007. Of these patients, 133 suffered from CRF at hospital admission (eGFR <40 mL/min/1.73 m2 body surface and/or serum creatinine >2 mg/dL). During hospitalization for AMI, the CRF-affected patients showed a 2.7 times higher relative risk of mortality than patients without CRF (Yates chi square 14.46; p = 0.0001432). The evaluated comorbidities (hypertension, type 2 diabetes, supra-aortic vascular stenosis >70%, previous PTCA, COPD, previous AMI, previous coronary artery bypass and chronic obliterative peripheral arteriopathy) increased the relative risk of death 1.2- to 3.76-fold in those affected. In accord with recent evidence in the international literature, our results point to the importance of early assessment of CRF for the prognosis of patients with AMI.

Opioids for neonates receiving mechanical ventilation.

BACKGROUND: Mechanical ventilation is a potentially painful and discomforting intervention widely used in neonatal intensive care units. Newborn babies (neonates) demonstrate increased sensitivity to pain, which may affect clinical and neurodevelopmental outcomes. The use of drugs that reduce pain might be important in improving survival and neurodevelopmental outcomes. OBJECTIVES: To determine the effect of opioid analgesics (pain-killing drugs derived from opium e.g. morphine), compared to placebo, no drug, or other non-opioid analgesics or sedatives, on pain, duration of mechanical ventilation, mortality, growth and neurodevelopmental outcomes in newborn infants on mechanical ventilation. SEARCH STRATEGY: Electronic searches included: the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007); MEDLINE (1966 to June 2007); EMBASE (1974 to June 2007); and CINAHL (1982 to 2007). Previous reviews and lists of relevant articles were cross-referenced. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials comparing opioids to a control, or to other analgesics or sedatives in newborn infants on mechanical ventilation. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two review authors. Categorical outcomes were analysed using relative risk and risk difference; and continuous outcomes with weighted mean difference or standardised mean difference. A fixed effect model was used for meta-analysis except where heterogeneity existed, in which case a random effects model was used. MAIN RESULTS: Thirteen studies on 1505 infants were included. Infants given opioids showed reduced premature infant pain profile (PIPP) scores compared to the control group (weighted mean difference -1.71; 95% confidence interval -3.18 to -0.24). Differences in execution and reporting of trials mean that this meta-analysis should be interpreted with caution. Heterogeneity was significantly high in all analyses of pain, even when lower quality studies were excluded and analysis limited to very preterm newborns. Meta-analyses of mortality, duration of mechanical ventilation, and long and short-term neurodevelopmental outcomes showed no statistically significant differences. Very preterm infants given morphine took significantly longer to reach full enteral feeding than those in control groups (weighted mean difference 2.10 days; 95% confidence interval 0.35 to 3.85). One study compared morphine with a sedative: the treatments showed similar pain scores, but morphine had fewer adverse effects. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend routine use of opioids in mechanically ventilated newborns. Opioids should be used selectively, when indicated by clinical judgment and evaluation of pain indicators. If sedation is required, morphine is safer than midazolam. Further research is needed.

Accuracy of telomerase in cervical lesions: a systematic review.

The detection of telomerase activity in cervix may provide information on cervical carcinogenesis and may be a marker to monitor cervical intraepithelial neoplasia transition. A quantitative systematic review was performed to estimate the accuracy of telomerase assay in cervical lesions. Studies that evaluated the telomerase test (telomerase repeated amplification protocol) for the diagnosis of cervix lesions and compared it to paraffin-embedded sections as the diagnostic standard were included. Ten studies were analyzed, which included 1069 women. The diagnostic odds ratio (DOR) for a positive telomerase test for low-grade squamous intraepithelial lesions (Lo-SIL) vs normal or benign lesions was 3.2 (95% CI, 1.9-5.6). The DOR for a positive telomerase test for high-grade squamous intraepithelial lesions (Hi-SIL) vs Lo-SIL, normal or benign lesions was 5.8 (95% CI, 3.1-10). For cervix cancer vs Hi-SIL, the DOR for a positive telomerase test was 8.1 (95% CI, 3.2-20.3) and for cervix cancer vs Lo-SIL, normal or benign lesions, it was 40.9 (95% CI, 18.2-91). Our data support the current hypothesis that telomerase may activate an early event in cervical carcinogenesis that could be associated with the initiation and progression of cervical lesions.

No reflow in patients undergoing primary angioplasty for acute myocardial infarction at high risk: incidence and predictive factors.

AIM: Percutaneous coronary intervention (PCI) is a consolidated therapeutic strategy for the treatment of acute myocardial infarction (AMI), but achieving a TIMI 3 flow does not always correspond to true tissue reperfusion. The aim of the study was to evaluate the incidence and predictive factors of no reflow in patients undergoing primary angioplasty (PCI) for AMI at high risk, in the setting of a provincial cardiological emergency network. METHODS: We retrospectively analyzed the ECGs of 360 consecutive patients undergoing primary PCI, between 2001-2004, recorded before and 90 min after the procedure, and compared them with the angiographic data. RESULTS: The patients were divided into 2 groups: group A (reperfused) with a >50% reduction in ST and group B (no reflow) with a <50% reduction in ST but a TIMI 3 flow in the epicardial vessel. The 2 groups were comparable in terms of mean age, sex, diabetes and AMI site. However, there were statistically significant differences between the groups in terms of precoronary time, Killip class IV, ejection fraction, mean leukocyte count, C-reactive protein, and the periprocedural administration of abciximab. Total mortality was 6%: 14% in group B vs 3% in group A. CONCLUSIONS: Our data show that a fair percentage of patients (24%) with a TIMI 3 flow after PCI during ST-elevation MI do not show ECG signs of effective reperfusion and have a higher in-hospital mortality rate. Precoronary time and the inflammatory phlogistic substrate are important independent predictors of no reflow. Pretreatment with abciximab, particularly if it is not periprocedural, can prevent the occurrence of no reflow.

[Coronary disease: early intervention saves lives. Treatment of acute myocardial infarction in Mantova: results of thirty months of work after the implementation of a province network]. / Malattia coronarica: l'intervento precoce salva la vita. Terapia dell'infarto miocardico acuto a Mantova, risultati di trenta mesi di attivita' dopo l'attivazione di una rete provinciale.

BACKGROUND: Since June 2001, in the province of Mantova, we have undertaken a program for the management of acute myocardial infarction based on the early assessment of patient risk profiles, concerning telematic connections among care centers and on the optimization of in-hospital and out of hospital critical pathways for access to care. MATERIALS AND METHODS: Our network provides connections among the following centers: advanced life support ambulances, seven hospitals, three coronary care units, one cath lab on call 24 h a day for primary angioplasty, and one thoracic surgery division. This program, through its strong telematic platform, allows the early assessment of myocardial infarction and provides primary angioplasty to all high-risk patients, as fibrinolytic treatment is reserved only for low-risk patients admitted in peripheral hospitals. RESULTS: Two hundred and eighty patients with acute myocardial infarction were treated with angioplasty; 224 patients (80%) underwent primary angioplasty, 36 patients (13%) facilitated angioplasty and 20 patients (7%) rescue angioplasty. One hundred and thirty-two patients (47%) were first admitted to Mantova Hospital; 78 patients (28%) were referred to Mantova from peripheral hospitals and 70 patients (25%) were directly transported to the cath lab by advanced life support ambulances. Procedural success was obtained in 98% of patients, with 0.4% intraprocedural mortality. In-hospital mortality was 5.7%, while mortality in cardiogenic shock patients was 36%. The recurrence of acute myocardial infarction occurred in 1% of patients and major bleeding occurred in 2.2% of patients. One patient with cardiogenic shock died during transport. Mean door to balloon time was 67 min with a 42% reduction in the 3rd recruitment period. CONCLUSIONS: This program, developed in the setting of a provincial network for the management of acute myocardial infarction, provided primary angioplasty to all high-risk patients, with a high procedural success rate. Within a few months, time to treatment was minimized by the use of telematic facilities.

Opioids for neonates receiving mechanical ventilation.

BACKGROUND: Mechanical ventilation is a potentially painful intervention widely used in neonatal intensive care units. Since newborn babies (neonates) demonstrate increased sensitivity to pain, which may affect clinical and neurodevelopmental outcomes, the use of drugs which reduce pain might be very important. OBJECTIVES: To determine the effect of opioid analgesics (pain-killing drugs derived from opium e.g. morphine), compared to placebo, no drug, or other non-opioid analgesics or sedatives, on pain, duration of mechanical ventilation, mortality, growth and neurodevelopmental outcomes in newborn infants on mechanical ventilation. SEARCH STRATEGY: Electronic searches included: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2004); MEDLINE (1966 to June 2004); EMBASE (1974 to June 2004); and CINAHL (1982 to 2003). Previous reviews and lists of relevant articles were cross-referenced. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials comparing opioids to a control, or to other analgesics or sedatives in newborn infants on mechanical ventilation. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers independently. Categorical outcomes were analysed using relative risk and risk difference; and continuous outcomes with weighted mean difference or standardised mean difference. A fixed effect model was used for meta-analysis except where heterogeneity existed, when a random effects model was used. MAIN RESULTS: Thirteen studies on 1505 infants were included. Infants given opioids showed reduced premature infant pain profile (PIPP) scores compared to the control group (weighted mean difference -1.71; 95% confidence interval -3.18 to -0.24). Differences in execution and reporting of trials mean that this meta-analysis should be interpreted with caution. Heterogeneity was significantly high in all analyses of pain, even when lower quality studies were excluded and analysis limited to very preterm newborns. Meta-analyses of mortality, duration of mechanical ventilation, and long and short term neurodevelopmental outcomes showed no statistically significant differences. Very preterm infants given morphine took significantly longer to reach full enteral feeding than those in control groups (weighted mean difference 2.10 days; 95% confidence interval 0.35 to 3.85). One study compared morphine with a sedative: the treatments showed similar pain scores, but morphine had fewer adverse effects. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend routine use of opioids in mechanically ventilated newborns. Opioids should be used selectively, when indicated by clinical judgment and evaluation of pain indicators. If sedation is required, morphine is safer than midazolam. Further research is needed.

Determination of oxidative status in breast and formula milk.

AIM: To investigate to what extent formula milk and stored breast milk, commonly used in hospitals, could be pro-oxidant sources for newborn babies. METHODS: We determined total antioxidant capacity and lipid peroxidation products, such as lipid peroxides, TBARS and conjugated dienes, in fresh and stored (at -20 degrees C) samples of breast milk and in different brands of formula milk. RESULTS: There were notable differences in the oxidation parameters in several brands of formula milk, particularly concerning the levels of lipid peroxides and total antioxidant capacity. No difference was found in the mean total antioxidant capacity between formula and breast milk, even if the vitamin content is much higher in formula milk than in breast milk. On the contrary, all the considered lipid peroxidation products were higher in human milk (HM) than formula milk (FM), and lipid peroxides were much higher in HM stored at -20 degrees C. Many differences were found between different formula milks. CONCLUSION: There was a conspicuous formation of lipid peroxides in HM stored at -20 degrees C, which was probably caused by an increased presence of free fatty acids due to lipoprotein lipase activity during storage. Unexpectedly, even fresh HM had a higher concentration of lipid peroxidation products when compared to FM. This could be ascribed to the higher susceptibility of HM to degradation during analysis because of manipulation and light exposure. However, it is also interesting that the high content of lipid peroxides did not correspond to a low total antioxidant capacity in either breast or formula milk. This could signify that such levels of lipid peroxidation products might be present naturally in milk and HM after expression is subject to a strong peroxidation either at room temperature or at -20 degrees C.

[Etiopathogenesis of acute myocardial infarction: role of early leukocytosis]. / Eziopatogenesi dell'infarto miocardico acuto. Ruolo della leucocitosi precoce.

It has recently been suggested that inflammation may play an important role in the pathogenesis of acute ischemic syndromes. It may therefore be important to relate their clinical features with plasma indexes of inflammation. We have studied leukocyte, platelet and fibrinogen blood levels in 57 consecutive patients with acute myocardial infarction admitted to our Intensive Care Unit within 90 min after the onset of chest pain and treated with primary coronary angioplasty. Patients were divided into two groups on the basis of blood leukocyte levels: Group A, 24 patients, 17 males, mean age 54.2 +/- 13.7 years, with high blood leukocytes and Group B, 33 patients, 28 males, mean age 60.9 +/- 10.3 years, with normal blood leukocytes. Group A patients also had higher serum fibrinogen (p = 0.05) and blood platelet levels (p < 0.05). The stenosis observed after guidewire advancement was significant (> 75%) in 33% of the patients with leukocytosis vs 94% of the others (p < 0.01). No difference between the two groups was observed in the success rate of coronary angioplasty and prevalence of stent placement (100 vs 97%, and 43 vs 42% of the patients of Group A and B, respectively). In contrast, a tendency to rethrombosis requiring Rheopro administration was observed in 62% Group A patients vs 21% Group B patients (p < 0.01). In conclusion, the finding of leukocytosis in the acute phase of myocardial infarction suggests that coronary occlusion is mainly caused by a coronary thrombus occurring at the site of a non significant stenosis. In contrast, when blood leukocytes are normal, the underlying coronary stenosis is more often critical and the thrombotic process is less important. The high blood leukocytes, platelet and fibrinogen levels of Group A patients are consistent with a significant role of inflammation in the pathogenesis of the thrombotic process while hemodynamic and local mechanical factors are probably more important in patients with normal blood leukocytes.

'Dual positivity' for neural tube defects and down syndrome at maternal serum screening: gestational outcome.

OBJECTIVE: To evaluate the gestational outcome of pregnancies screen-positive for both neural tube defects (NTD) and Down syndrome (DS) ('dual positivity'). METHODS: Among 10,667 mid-trimester women screened for DS and NTD with alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG), delivered up to July 1996, we have selected cases with both an unexplained AFP value > or = 2.5 multiples of median (MoM) and a DS risk > or = 1:250. All these pregnant women were managed with amniocentesis and/or CVS, ultrasound scans, and Doppler velocimetry. We have collected all data about the gestations with 'dual positivity' and no obvious explanation for these findings (cases with fetal malformations related to raised AFP). RESULTS: Twelve women (1.1:1,000) showed unexplained 'dual positivity'. Abnormal karyotypes were found in 3 fetuses, and pregnancies were terminated: there were 2 triploidies with partial hydatiform mola, and 1 DS. In 9 cases the fetal karyotype was normal, but a confined placental trisomy 16 was found in 4. Of the 9 continuing gestations, 8 displayed fetal growth retardation (FGR). One gestation ended with fetal death at 27 weeks. All 9 fetuses were morphologically normal, and 8 were small for gestational age. CONCLUSIONS: 'Dual positivity' at NTD/DS screening may anticipate pregnancy complications. The finding of trisomy 16 confined to the placenta and FGR in 4 cases suggests that at least some fetuses with growth restriction may suffer from a distinct placental disease. Maternal serum screening may have implications different from DS and NTD, as demonstrated by the 2 cases with triploidy and incomplete hydatiform mola, the 4 cases with placental trisomy 16, and the 4 cases of FGR of the 5 fetuses without chromosome abnormalities. As the pathologic outcome of these pregnancies is more important than the mere serum screening results, we feel that these cases need a strict work-up, including CVS, amniocentesis and ultrasound studies to better address the obstetrical management.

Effects of neurohormonal antagonism on symptoms and quality-of-life in heart failure.

Increased mortality and reduced functional capacity are the two main characteristics of chronic heart failure. Activation of the renin-angiotensin and sympathetic systems has a primary role in the progressive worsening of heart failure and increased mortality of patients. In addition, both systems may be important in the pathogenesis of exercise intolerance, although there is only a weak relationship between neurohormonal activation and exercise capacity. While neurohormonal antagonists, such as angiotensin-converting enzyme (ACE) inhibitors and beta-blockers, consistently improve the prognosis of patients with heart failure, their effects on exercise tolerance have often been less significant. This problem has been emphasized by the introduction of beta-blockers for the therapy of heart failure. Beta blockade results in a significant improvement in left ventricular function during rest and exercise. However, the reduction in chronotropic response to exercise as well as the metabolic changes caused by these agents in skeletal muscle may result in an apparent lack of change in maximal functional capacity. This effect is particularly important with the new third generation non-selective beta-blockers. The pronounced anti-adrenergic activity of these compounds accounts for their greater negative chronotropic effect and relates to the lack of improvement in peak oxygen consumption (VO2). Submaximal exercise testing can be used to assess changes induced by these agents. However, even the six-minute walk test may act as an almost maximal test in patients with advanced heart failure: moreover, the measurement of submaximal exercise duration may be sensitive enough to detect changes in single-centre trials, but not in multicentre trials. To date, direct assessment of symptoms by both patient and physician is still the most sensitive tool to monitor changes in functional status with non-selective beta-blockers. Thus, an accurate method of measuring patients' symptoms, in addition to the clinical examination, is still necessary when neurohormonal antagonists are used in patients with chronic heart failure.