Parents spend an average of nine hours a day providing palliative care for children at home and need to maintain an average of five life-saving devices.

AIM: This Italian study investigated home-based palliative care for young children and how long it took parents to meet their needs. METHODS: The study population consisted of 33 families with a child under the responsibility of the Veneto Regional Center for Pediatric Palliative Care, northern Italy, who needed medical support in at least two of the following areas: respiratory, feeding, pain and seizures. RESULTS: The children had a mean age of 6.8 ± 4.7 years. We found that 72% of the patients needed medical devices for feeding, 36% had a tracheostomy and 55% were on mechanical ventilatory support. The children needed an average of five different life-supporting medical appliances, and the time taken to provide for their care increased significantly with each additional appliance (p = 0.016). Their most time-consuming daily needs were feeding (174 minutes) and support when they woke up at night (67 minutes). The average daily time that parents spent taking care of their child amounted to eight hours and 54 minutes per day. CONCLUSION: Parents providing palliative care for children with life-limiting diseases spent an average of nine hours a day caring for them each day and had to maintain an average of five medical appliances.

Comprehensive protocol of traceability during IVF: the result of a multicentre failure mode and effect analysis.

STUDY QUESTION: Can traceability of gametes and embryos be ensured during IVF? SUMMARY ANSWER: The use of a simple and comprehensive traceability system that includes the most susceptible phases during the IVF process minimizes the risk of mismatches. WHAT IS KNOWN ALREADY: Mismatches in IVF are very rare but unfortunately possible with dramatic consequences for both patients and health care professionals. Traceability is thus a fundamental aspect of the treatment. A clear process of patient and cell identification involving witnessing protocols has to be in place in every unit. To identify potential failures in the traceability process and to develop strategies to mitigate the risk of mismatches, previously failure mode and effects analysis (FMEA) has been used effectively. The FMEA approach is however a subjective analysis, strictly related to specific protocols and thus the results are not always widely applicable. To reduce subjectivity and to obtain a widespread comprehensive protocol of traceability, a multicentre centrally coordinated FMEA was performed. STUDY DESIGN, SIZE, DURATION: Seven representative Italian centres (three public and four private) were selected. The study had a duration of 21 months (from April 2015 to December 2016) and was centrally coordinated by a team of experts: a risk analysis specialist, an expert embryologist and a specialist in human factor. Principal investigators of each centre were first instructed about proactive risk assessment and FMEA methodology. A multidisciplinary team to perform the FMEA analysis was then formed in each centre. After mapping the traceability process, each team identified the possible causes of mistakes in their protocol. A risk priority number (RPN) for each identified potential failure mode was calculated. The results of the FMEA analyses were centrally investigated and consistent corrective measures suggested. The teams performed new FMEA analyses after the recommended implementations. PARTICIPANTS/MATERIALS, SETTING, METHODS: In each centre, this study involved: the laboratory director, the Quality Control & Quality Assurance responsible, Embryologist(s), Gynaecologist(s), Nurse(s) and Administration. The FMEA analyses were performed according to the Joint Commission International. MAIN RESULTS AND THE ROLE OF CHANCE: The FMEA teams identified seven main process phases: oocyte collection, sperm collection, gamete processing, insemination, embryo culture, embryo transfer and gamete/embryo cryopreservation. A mean of 19.3 (SD ± 5.8) associated process steps and 41.9 (SD ± 12.4) possible failure modes were recognized per centre. A RPN ≥15 was calculated in a mean of 6.4 steps (range 2-12, SD ± 3.60). A total of 293 failure modes were centrally analysed 45 of which were considered at medium/high risk. After consistent corrective measures implementation and re-evaluation, a significant reduction in the RPNs in all centres (RPN <15 for all steps) was observed. A simple and comprehensive traceability system was designed as the result of the seven FMEA analyses. LIMITATIONS, REASONS FOR CAUTION: The validity of FMEA is in general questionable due to the subjectivity of the judgments. The design of this study has however minimized this risk by introducing external experts for the analysis of the FMEA results. Specific situations such as sperm/oocyte donation, import/export and pre-implantation genetic testing were not taken into consideration. Finally, this study is only limited to the analysis of failure modes that may lead to mismatches, other possible procedural mistakes are not accounted for. WIDER IMPLICATIONS OF THE FINDINGS: Every single IVF centre should have a clear and reliable protocol for identification of patients and traceability of cells during manipulation. The results of this study can support IVF groups in better recognizing critical steps in their protocols, understanding identification and witnessing process, and in turn enhancing safety by introducing validated corrective measures. STUDY FUNDING/COMPETING INTEREST(S): This study was designed by the Italian Society of Embryology Reproduction and Research (SIERR) and funded by the Italian National Transplant Centre (CNT) of the Italian National Institute of Health (ISS). The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Sedoanalgesia in paediatric intensive care: a survey of 19 Italian units.

AIM: To analyse the methods used to manage and monitor sedoanalgesia at Italian paediatric intensive care units (ICUs). METHODS: Data were collected by administering a questionnaire that aimed to investigate whether ICUs adopted a validated protocol to manage sedoanalgesia. RESULTS: The results revealed that a majority of the ICUs adopt a protocol for dealing with sedation and analgesia, but this protocol is implemented with difficulty or not at all in routine clinical practice. The most often used pharmacological combination, is midazolam and fentanyl. Several weaknesses remain in terms of the methods used to assess sedoanalgesia, which are generally not standardized, but rather based on recording the patient's physiological parameters. CONCLUSION: Sedation and analgesia are priority issues in the management of critically ill children. None of the numerous drugs available is ideal and the protocols currently used in clinical practice involve the combined use of different drugs. There is currently no shared and validated approach as to which is the most effective and safest sedoanalgesic regimen in critically ill children.

LH supplementation of ovarian stimulation protocols influences follicular fluid steroid composition contributing to the improvement of ovarian response in poor responder women.

In this prospective study, we evaluated the steroid levels in 111 follicular fluids (FF) collected from 13 women stimulated with FSH monotherapy and 205 FF collected from 28 women stimulated with FSH + LH because of a previous history of hypo-responsiveness to FSH. Steroid levels were measured by HPLC/MS-MS and related to ovarian stimulation protocol, oocyte maturity, fertilization and quality of blastocysts, after individually tracking the fate of all retrieved oocytes. 17-Hydroxy-Progesterone, Androstenedione, Estradiol and Estrone were significantly higher in the FSH + LH protocol. Progesterone, 17-Hydroxy-Progesterone and Estradiol were more expressed in FF yielding a mature oocyte (p < 0.01) in the FSH + LH protocol. FF Progesterone concentration was correlated with the rate of normal fertilization in the FSH protocol. None of the FF steroids measured were associated with blastocyst quality and achievement of pregnancy. Our results indicate that LH supplementation in hypo-responsive women modifies ovarian steroid production, mimicking physiological production better and likely contributing to an improved ovarian response. Employing a correct methodological procedure to evaluate the relationship between FF steroid hormones and assisted reproduction outcomes, our study reveals that some steroids in single follicles may be helpful in predicting oocyte maturity and fertilization.

The Italian version of the PedsQL in children with rheumatic diseases.

OBJECTIVE: The aim of the study was to test the reliability and validity of the Italian translation of the PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Rheumatologic Module in a sample of rheumatologic children in Italy. METHODS: The PedsQL 4.0 and the PedsQL 3.0 were administered to rheumatic and healthy children. 102 children 5-18 years old and 132 parents of children 2-18 years old were tested. Additionally, the Child Health Questionnaire - Parent Form 50 - was administered to the rheumatologic sample. RESULTS: Internal consistency reliability for group comparisons reached the recommended coefficient alpha of 0.70 for PedsQL 4.0 and PedsQL 3.0. The inter-correlation between these last ones was highly significant. The correlation between the PedsQL 4.0 and the CHQ was statistically significant. CONCLUSION: The Italian version of the PedsQL 4.0 and PedsQL 3.0 Rheumatology Module demonstrate acceptable reliability and validity for both patient self-report and parent proxy-report.

Chromatin Protamination and Catsper Expression in Spermatozoa Predict Clinical Outcomes after Assisted Reproduction Programs.

Identification of parameters predicting assisted reproductive technologies (ARTs) success is a major goal of research in reproduction. Quality of gametes is essential to achieve good quality embryos and increase the success of ARTs. We evaluated two sperm parameters, chromatin maturity and expression of the sperm specific calcium channel CATSPER, in relation to ART outcomes in 206 couples undergoing ARTs. Chromatin maturity was evaluated by Chromomycin A3 (CMA3) for protamination and Aniline Blue (AB) for histone persistence and CATSPER expression by a flow cytometric method. CMA3 positivity and CATSPER expression significantly predicted the attainment of good quality embryos with an OR of 6.6 and 14.3 respectively, whereas AB staining was correlated with fertilization rate. In the subgroup of couples with women ≤35 years, CATSPER also predicted achievement of clinical pregnancy (OR = 4.4). Including CMA3, CATSPER and other parameters affecting ART outcomes (female age, female factor and number of MII oocytes), a model that resulted able to predict good embryo quality with high accuracy was developed. CMA3 staining and CATSPER expression may be considered two applicable tools to predict ART success and useful for couple counseling. This is the first study demonstrating a role of CATSPER expression in embryo development after ARTs programs.

Circulating ghrelin level is increased in coeliac disease as in functional dyspepsia and reverts to normal during gluten-free diet.

BACKGROUND: It is controversial whether serum ghrelin concentration is altered in coeliac disease and whether this alteration is related to nutritional impairment or to inflammatory changes of duodenal mucosa. AIM: To investigate clinical and histopathological variables affecting circulating ghrelin in coeliac patients by comparison with dyspeptic patients and with healthy controls. METHODS: We measured serum ghrelin and obtained gastric and duodenal biopsies in 44 coeliac patients before and after 1-year gluten-free diet, in 39 dyspeptic patients and 53 healthy controls. RESULTS: Serum ghrelin concentration was significantly higher in coeliac (531 +/- 29 pg/mL, P < 0.05) and in dyspeptic patients (526 +/- 14 pg/mL, P < 0.01) than in healthy controls (451 +/- 8 pg/mL), and body mass index was significantly lower in coeliac (20 +/- 1) and in dyspeptic patients (20 +/- 1) than in healthy controls (22 +/- 1, P < 0.05). In coeliac patients serum ghrelin concentration was not related to the severity of duodenal lesions. Serum ghrelin reverted to normal (399 +/- 30 pg/mL) and body mass index increased significantly (0.6 +/- 0.1 kg/m(2) increase, P < 0.05) during gluten-free diet despite persistent duodenal lymphocytic infiltration. CONCLUSIONS: Ghrelin concentration is increased and body mass index is decreased in coeliac and in dyspeptic patients irrespective of presence and severity of duodenal inflammation. Nutritional impairment is a key factor in elevating plasma ghrelin levels in coeliac disease.

Detection of an anti-RhD antibody 2 years after sensitization in a patient who had undergone an allogeneic BMT.

We describe an HLA matched bone marrow transplantation with minor ABO incompatibility and RhD mismatch (donor RhD negative and recipient RhD positive). GVHD appeared on day +96 and therapy with steroid and cyclosporin was started. When GVHD disappeared and immunosuppressive therapy was stopped (2 years after BMT), an anti-RhD antibody was detected in the patient's serum. The delayed appearance of this antibody may have been associated with the prolonged immunosuppression that was required for treatment of the patient's GVHD.

Value of measuring gallbladder motility in clinical practice.

Measurement of gallbladder motility is a powerful research tool, but its value in clinical practice is uncertain. Three main conditions have been investigated for potential clinical application of this measurement. The first potential application is for identification of patients at risk of recurrence following gallstone dissolution with medical therapy. Results in this clinical setting are disappointing due to the low positive predictive value for gallstone recurrence in sluggish gallbladder emptying. The second potential application is for identification of obese patients at risk of gallstone formation during rapid weight loss. In this condition, a high negative predictive value has been reported for a normal gallbladder emptying pattern. The third potential application is for patients with recurrent biliary colic and acalcolous gallbladder disease. The diagnostic value of a provocative test involving intravenous cholecystokinin injection as a method of identifying patients likely to benefit from cholecystectomy is uncertain, partly as a consequence of non-standardized methodology. The balance of evidence reported in this review suggests a low inherent value of measurement of gallbladder motility in clinical practice. Acalcolous gallbladder disease is the clinical setting deserving further investigation on the value of the cholecystokinin provocative test, but this test needs to be standardized.

Survival rate and prognostic factors in patients with intestinal failure.

BACKGROUND: Intestinal failure impairs nutritional status and survival expectance. Though intestinal adaptation and enteral independence may be achieved, artificial nutrition is needed in about half of the patients. AIMS: This study is aimed at assessing the causes of death, survival rate, enteral independence in time, and factors affecting the clinical outcome in a group of patients with intestinal insufficiency. PATIENTS: Sixty-eight patients with intestinal insufficiency, due to major intestinal resection in 60 cases (short bowel syndrome) (remnant intestine length 101-150 cm in 31 cases, 50-100 cm in 23 cases, <50 cm in 6 cases), and due to chronic idiopathic pseudo-obstruction in 8 cases, were enrolled and followed-up for (median) 36 months (25th and 75th percentile in 12 and 60 months, respectively). In 60 short bowel syndrome patients, the main conditions that led to intestinal failure were ischemic bowel (28), major surgery complications or severe adhesions (17), radiation enteritis (10), Chron's disease, intestinal tuberculosis, small bowel lymphoma and trauma (others). METHODS: Seventeen variables age, underlying disorders, length of remnant bowel, type of surgery, hospital stay, type of nutrition (hospital and home) and its variations in time, causes of death, survival rate and time were considered. Statistical analysis was carried out by Mann-Whitney U-test, Pearson chi2, Spearman correlation test, Kaplan-Meyer method and Cox's proportion hazards regression model. RESULTS: At the time of admission to the hospital, none of the patients had nutritional independence, 54 (79.4%) were on parenteral nutrition and 14 (20.6%) were on enteral nutrition. At the time of discharge, 23 (33.8%) patients showed enteral independence, 39 were on home parenteral nutrition, 3 on enteral nutrition + i.v. feeding, 1 on enteral nutrition, and 2 needed oral supplementation with hydroelectrolyte solutions only. After a median value of 36 months, 30 and 2 patients were on home parenteral nutrition and enteral nutrition + i.v. feeding, respectively, 2 on enteral nutrition, 2 on oral supplementation with hydroelectrolyte solutions, and 26 cases reached enteral independence. A significant relationship was detected between the length of remnant bowel and types of nutrition at both admission (r = 0.38; P = 0.001) and discharge (r = 0.48; P = 0.001), parenteral nutrition being more frequent in patients with very short bowel. Twenty-two patients (32.4%) died (4 from newly occurring malignancies), 40 (58.8%) survived, and 6 (8.8%) were lost to the follow-up. Eleven of 22 patients died from conditions related to intestinal failure (8 cases) and/or home parenteral nutrition complications (3 cases). At 12, 24, 36, 48, 60 and 72 months, survival rates were 95.4, 93.3, 88.1, 78.6, 78.6 and 65.5%, respectively, but it was significantly lower for patients with <50 cm of remnant bowel than those with longer residual intestine (P < 0.05), and in patients who started home parenteral nutrition above the age of 45 years (P < 0.02). Survival rate was higher in patients with enteral independence than those with enteral dependence (P < 0.05). Better survival rates were registered in patients with chronic obstructive intestinal pseudo-obstruction and major surgery complications, whereas ischemic bowel and even more radiation enteritis were associated with a lower survival expectance. CONCLUSIONS: Actuarial survival rate of patients with intestinal failure quotes 88 and 78% at 3 and 5 years, respectively. It is influenced by the length of remnant intestine, age at the start of home parenteral nutrition, enteral independence and, to some extent at least, by the primary disorder. Enteral independence can be achieved in time by about 40% of the patients with intestinal insufficiency, but for home parenteral nutrition-dependent cases, intravenous feeding can be stopped in less than one out of five patients during a median 3-year period.

Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease.

AIM: To evaluate the effects of low dose fentanyl infusion analgesia on behavioural and neuroendocrine stress response and short term outcome in premature infants ventilated for hyaline membrane disease. METHODS: Twenty seven ventilated preterm infants were randomly assigned to receive a mean fentanyl infusion of 1.1 (0.08 SE) micrograms/kg/h for 75 (5) hours, and 28 untreated infants were considered a control group. A behavioural sedation score was used to assess the infants' behaviour. Urinary metanephrine and the normetanephrine:creatinine molar ratio were determined at 0, 24, 48 and 72 hours. Outcome data and ventilatory indexes were recorded for each infant. RESULTS: The fentanyl group showed significantly lower behavioural stress scores and O2 desaturations than controls and lower urinary concentrations of metanephrine and normetanephrine at 24, 48, 72 hours. The two groups showed no significant difference in ventilatory variables or short term outcome. CONCLUSIONS: A short course of low dose fentanyl infusion reduces behavioural sedation scores, O2 desaturations and neuroendocrine stress response in preterm ventilated infants.

Metabolic and respiratory effects of theophylline in the preterm infant.

BACKGROUND: Methylxanthines are often administered to preterm infants for the treatment of apnoea. AIMS: To study the effects of theophylline on energy metabolism, physical activity, and lung mechanics in preterm infants. METHODS: Indirect calorimetry was performed for six hours before and after administration of a bolus of theophylline (5 mg/kg) in 18 preterm infants while physical activity was recorded with a video camera. Lung mechanics measurements were performed at baseline and 12 and 24 hours after theophylline treatment. RESULTS: Theophylline increased mean (SEM) energy expenditure by 15 (5) kJ/kg/day and augmented carbohydrate utilisation from 6.8 to 8.0 g/kg/day, but fat oxidation was unchanged. After theophylline treatment, preterm infants had faster respiration, lower transcutaneous CO2, and improved static respiratory compliance without increased physical activity. CONCLUSIONS: A bolus of 5 mg/kg theophylline increased energy expenditure independently of physical activity, increased carbohydrate utilisation, and improved respiratory compliance. The increased energy expenditure could be detrimental to the growth of the preterm infant.

Attention and reaction to distress in infancy: a longitudinal study.

The primary aim of this study was to verify whether early individual differences in look duration are related to general mechanisms of the infant nervous system that draw together attention and emotion. Thirty-one infants were observed at 3, 5, and 11 months of age. Facial expressions of pain and distress were observed by means of C. Izard's (1979) Maximally Discriminative Facial Movement Coding System 90 s after routine pediatric vaccinations. Several measures of visual attention were taken experimentally in a separate testing session. Significant correlations between measures of attention and duration of facial expressions of pain and distress were found at each age level. Infants who showed pain or distress for a shorter time period also paid attention for a shorter time period and vice versa. The main conclusion is that individual differences combining control of both pain and attention can be identified from early infancy.

Empiric therapy of infections in hematologic malignancies: a prospective, randomized trial.

Patients with hematologic malignancies were randomly assigned to receive cefuroxime (group A) or tobramycin plus ampicillin (Group B) during 86 febrile episodes. In both regimens carbenicillin was added during neutropenia (71% of all episodes: groups C and D). The most common type of infection was pneumonia (48% alone; 72% with other sites involved), which accounted for a high fatality rate (15%); the highest rate occurred during septicemia with pneumonia (50%). The overall response rate to initial therapy was 63% without significant differences among the four regimens. The worst prognosis was observed in neutropenic patients without granulocyte recovery. When initial and cross-over trials were combined, there were favorable outcomes in 90% of all cases. Cefuroxime alone seems to be as effective as tobramycin plus ampicillin in the treatment of infections in hematologic malignancies. No side effects could be attributed to the cefuroxime-containing regimens.

Evaluation of the scintigraphic technique for detecting bone metastases in 100 breast cancer patients.

In an attempt to evaluate the utility of bone scintigraphy for the diagnosis and follow-up of skeletal metastases, radioisotopic scan (total body) by 99mTc has been performed on 100 patients suffering from breast cancer in various stages. The radiographic control followed the scan on the basis of clinical or scintigraphic suspicion of bone lesions. Twenty-one patients showed metastases by scan, and in all but 2 the radiography was concordantly positive; in 22 subjects scintigraphy and radiology demonstrated non-malignant lesions. Both scan and radiology were used to explore 169 metastatic localizations, with concordant results in 45% of the sites; however, 7% of the sites with discordant results became positive for metastasis by radiology some months after the scan positivity. The false-negative results were more frequent in the radiographic study (27%) than with the scintigraphic scan (21%). The latter technique was unable to detect osteoblastic lesions in particular. The scintigraphic test also gave reliable results in the follow-up procedure, frequently anticipating the radiological modifications of metastatic lesions. In conclusion, bone scan often appears to be more accurate and preocious than the roentgengraphic test in the detection and the follow-up of skeletal metastatic lesions; it suggests the utility of the bone scan as a preliminary test, which allows a more rational use of the radiology.

[Antithrombin activity during estroprogestin therapy]. / Attività antitrombinica durante la terapia estroprogestinica.

PIP: 50 women on estroprogestational contraceptive treatment, and 48 healthy controls were observed to examine antithrombin activity, heparin-thrombin activity, and fibrinogen. Antithrombin activity and heparin-thrombin activity decreased significantly in women under OC (oral contraception) treatment, while fibrinogen did not increase significantly. No correlation was found between duration of therapy and antithrombin activity decrease. It is possible that there are 2 groups of women, one with normal antithrombin activity, and one with reduced activity; this last group of patients could be more at risk of hypercoagulation accidents, and should be checked more often.^ieng

Pain in infancy: individual differences.

Two patterns of reactions to painful medical procedures were found in infancy, i.e., continuous and interval patterns. Also, infants often in a good mood in everyday life (as reported by their mothers) showed pain more briefly after blood sampling, while infants often in a bad mood in everyday life showed pain longer.

[Noise exposure in neonatal intensive care units]. / Esposizione a rumore nelle terapie neonatali intensive.

This study evaluates the exposure of newborn babies in neonatal intensive care units (NICU) to noise which can cause hearing lesions directly (acoustic trauma) as well as indirectly (hypoxia). Moreover, noise can have an aggravating effect when combined with other potentially harmful factors in the NICU, such as ototoxic medication or stress due to other external stimuli, such as excessively bright light, lack of a day/night rhythm or pain. Sound pressure levels were measured in the NICU and inside the cribs in various experimental conditions, classified under 3 different types of sound events: constant background noise, variations in background noise and impulsive events. The main sources of noise detected were crib noise generated by ventilation and temperature control systems, ambient noise in the room, noise caused by the staff in the NICU, noise generated by crib alarm systems and NICU apparatus and noise caused by activity on the crib cover or on its plexiglas top. Findings revealed that the influence of ambient noise is fairly irrelevant. Background noise and its variations concerned with activities in the department never exceeded the limits considered potentially harmful to adults (DRC), whereas the impulsive noise generated by staff on the cribs or on the plexiglas tops was considerable and potentially harmful. These findings demonstrate that it is feasible and relatively easy to control noise in the NICU and significantly reduce the impulsive noise component by training staff to be more careful and avoid any unnecessary jolting and rough handling on and near the cribs.