Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children.

BACKGROUND: Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2-12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. METHODS: An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. RESULTS: 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13-5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063-7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. CONCLUSION: The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

Cardiac rehabilitation activities during the COVID-19 pandemic in Italy. Position Paper of the AICPR (Italian Association of Clinical Cardiology, Prevention and Rehabilitation).

The COVID-19 outbreak is having a significant impact on both cardiac rehabilitation (CR) inpatient and outpatient healthcare organization. The variety of clinical and care scenarios we are observing in Italy depends on the region, the organization of local services and the hospital involved. Some hospital wards have been closed to make room to dedicated beds or to quarantine the exposed health personnel. In other cases, CR units have been converted or transformed into COVID-19 units.  The present document aims at defining the state of the art of CR during COVID-19 pandemic, through the description of the clinical and management scenarios frequently observed during this period and the exploration of the future frontiers in the management of cardiac rehabilitation programs after the COVID-19 outbreak.

[The new concept of rehabilitation space in the era of the Digital Health in cardio-respiratory rehabilitation]. / Nuovo concetto di spazio riabilitativo nell'era della Digital Health in riabilitazione cardio-respiratoria.

SUMMARY: Rehabilitation Specialized Medicine offers new developments in relation to the new technologies, new demography, life expectation and chronicity. The same attention that in modern health systems is given to quality process and outcome, should also concern the hospital structural aspects, in order to humanize these spaces. In this perspective, the definition of a structure easy to access with well-defined areas within it, such us an external waiting area, reception area and work area, represents an integration which allows to achieve the goal of providing quality performance. The need of a new concept of rehabilitation space in the cardio-respiratory area, especially that of the Gymnasium, must be developed keeping in consideration the main scientific guidelines in cardio-respiratory field. Consequently, this will have four dedicated areas respectively to evaluation, aerobic training, strength training and educational, each one characterized by different colors. The abstract idea of "digital comprehensive rehabilitation", in which are inserted all rehabilitative services facilitated by the gym digitalization, are located in this context, and their main aim is to answer to the patient needs.

Cardiac Prevention and Rehabilitation "3.0": From acute to chronic phase. Position Paper of the ltalian Association for Cardiovascular Prevention and Rehabilitation (GICR-IACPR).

Cardiac rehabilitation (CR) is the subspecialty of clinical cardiology dedicated to the treatment of cardiac patients, early and in the long term after an acute event. The aim of CR is to improve both quality of life and prognosis through prognostic stratification, clinical stabilization and optimization of therapy (pharmacological and non), management of comorbidities, treatment of disability, as well as through the provision and reinforcement of secondary prevention interventions and maintenaince of adherence to treatment. The mission of CR has changed over time. Once centered on the acute phase, aimed primarily at short-term survival, the healthcare of cardiac patients now increasingly involves the chronic phase where the challenge is to guarantee continuity and quality of care in the medium and long-term. The aim of the present position paper is to provide the state-of-the-art of CR in Italy, discussing its trengths and weaknesses as well as future perspectives.

Comparison between IEGM-based approach and echocardiography in AV/PV and VV delay optimization in CRT-D recipients (Quicksept study).

BACKGROUND: AtrioVentricular (AV) and InterVentricular (VV) delay optimization can improve ventricular function in Cardiac Resynchronization Therapy (CRT) and is usually performed by means of echocardiography. St Jude Medical has developed an automated algorhythm which calculates the optimal AV and VV delays (QuickOpt™) based on Intracardiac ElectroGrams, (IEGM), within 2 min. So far, the efficacy of the algorhythm has been tested acutely with standard lead position at right ventricular (RV) apex. Aim of this project is to evaluate the algorhythm performance in the mid- and long-term with RV lead located in mid-septum. METHODS: AV and VV delays optimization data were collected in 13 centers using both echocardiographic and QuickOpt™ guidance in CRTD implanted patients provided with this algorhythm. Measurements of the aortic Velocity Time Integral (aVTI) were performed with both methods in a random order at pre-discharge, 6-month and 12-month follow-up. RESULTS: Fifty-three patients were studied (46 males; age 68 ± 10y; EF 28 ± 7%). Maximum aVTI obtained by echocardiography at different AV delays, were compared with aVTI acquired at AV delays suggested by QuickOpt. The AV Pearson correlations were 0.96 at pre-discharge, 0.95 and 0,98 at 6- and 12- month follow-up respectively. After programming optimal AV, the same approach was used to compare echocardiographic aVTI with aVTI corresponding to the VV values provided by QuickOpt. The VV Pearson Correlation were 0,92 at pre-discharge, 0,88 and 0.90 at 6-month and 12- month follow-up respectively. CONCLUSIONS: IEGM-based optimization provides comparable results with echocardiographic method (maximum aVTI) used as reference with mid-septum RV lead location.

Epstein-Barr virus load in children infected with human immunodeficiency virus type 1 in Uganda.

BACKGROUND: Epstein-Barr Virus (EBV) is involved in a wide range of malignancies, particularly in immunocompromised subjects. In Africa, EBV primary infection occurs during early childhood, but little is known about the EBV load in Human Immunodeficiency Virus type 1 (HIV-1)-infected children. METHODS: Blood samples from 213 HIV-1-infected children, 140 of whom were receiving antiretroviral therapy (ART), were collected at the Nsambya Hospital in Kampala, Uganda, and obtained for dried blood spot analysis. Nucleic acids were extracted and analyzed for quantification of EBV types 1 and 2; 16S ribosomal DNA (rDNA), a marker of microbial translocation; and HIV-1 RNA. RESULTS: Ninety-two of 140 children (66%) receiving ART and 57 of 73 ART-naive children (78%) had detectable EBV DNA levels. Coinfection with both EBV types was less frequent in ART-treated children than in ART-naive children (odds ratio, 0.54 [95% confidence interval {CI}, .30-.98]; P = .042). Mean EBV DNA levels (±standard deviation) were lower in the former (3.99 ± 0.59 vs 4.22 ± 0.54 log10 copies/mL; P = .006) and tended to be inversely associated with ART duration. EBV DNA levels were higher in children with an HIV-1 RNA load of > 3 log10 copies/mL of blood (regression coefficient, 0.32 [95% CI, .05-.59]; P = .020) and correlated with circulating 16S rDNA levels (rs = 0.25 [95% CI, .02-.46]; P = .031). CONCLUSIONS: These findings suggest that ART, by limiting HIV-1 replication, microbial translocation, and related immune activation, prevents superinfection with both EBV types and keeps EBV viremia down, thus potentially reducing the risk of EBV-associated lymphomas.

Viral load detection using dried blood spots in a cohort of HIV-1-infected children in Uganda: correlations with clinical and immunological criteria for treatment failure.

Correlations between clinical/immunological treatment failure and viral load (VL) detected by dried blood spot (DBS) sampling were explored in HIV-1-infected children in Uganda. Of 104 children on combined antiretroviral treatment (cART), 12.5% experienced clinical and/or immunological failure, while 28.8%, 44.2%, and 26.9% had VLs of <1,000, 1,000 to 5,000, and >5,000 copies/ml, respectively. Clinical/immunological failure poorly predicted virological failure.

[First definition of minimal care model: the role of nurses, physiotherapists, dietitians and psychologists in preventive and rehabilitative cardiology]. / Documento preliminare alla definizione degli interventi Minimal Care infermieristici, fisioterapici, dietistici e psicologici attuabili nell'ambito della Cardiologia Riabilitativa e Preventiva.

Rehabilitative and preventive cardiology (CRP) is configured as intervention prevention to "gain health" through a process of multifactorial care that reduces disability and the risk of subsequent cardiovascular events. It makes use of an interdisciplinary team in which every professional needs to have multiple intervention paths because of the different levels of clinical and functional complexity of cardiac patients who currently have access to the rehabilitation. The document refers to the use of interventions by nurses, physiotherapists, dietitians and psychologists that are part of the rehabilitation team of CRP. Interventions of which have been documented, on scientific bases and clinical practice, empirical effectiveness and organizational efficiency. The methodological approach of this paper is a first attempt to define, through the model of consensus, the minimum standards for a CRP evidence based characterized by clearly defined criteria that can be used by operators of CRP. The document describes the activities to be carried out in each of the phases included in the pathways of care by nurses, physiotherapists, dietitians and psychologists. The routes identified were divided, according to the type of patients who have access to the CRP and to the phases of care, including the initial assessment, intervention, evaluation and final reporting, in high medium and low complexity. Examples of models of reporting, used by the operators of the team according to the principles of good clinical practice, are provided. This is made to allow traceability of operations, encourage communication inside the working group and within the patient and the caregiver. Also to give any possible indication for the post-rehabilitation.

Adherence to antiretroviral therapy and acceptability of planned treatment interruptions in HIV-infected children.

There have been no paediatric randomised trials describing the effect of planned treatment interruptions (PTIs) of antiretroviral therapy (ART) on adherence, or evaluating acceptability of such a strategy. In PENTA 11, HIV-infected children were randomised to CD4-guided PTIs (n = 53) or continuous therapy (CT, n = 56). Carers, and children if appropriate, completed questionnaires on adherence to ART and acceptability of PTIs. There was no difference in reported adherence on ART between CT and PTI groups; non-adherence (reporting missed doses over the last 3 days or marking <100 % adherence since the last clinical visit on a visual analogue scale) was 18 % (20/111) and 14 % (12/83) on carer questionnaires in the CT and PTI groups respectively (odds ratios, OR (95 % CI) = 1.04 (0.20, 5.41), χ(2) (1) = 0.003, p = 0.96). Carers in Europe/USA reported non-adherence more often (31/121, 26 %) than in Thailand (1/73, 1 %; OR (95 % CI) = 54.65 (3.68, 810.55), χ(2) (1) = 8.45, p = 0.004). The majority of families indicated they were happy to have further PTIs (carer: 23/36, 64 %; children: 8/13, 62 %), however many reported more clinic visits during PTI were a problem (carer: 15/36, 42 %; children: 6/12, 50 %).

Evidence of Carotid Atherosclerosis Vulnerability Regression in Real Life From Magnetic Resonance Imaging: Results of the MAGNETIC Prospective Study.

Background Atherosclerosis vulnerability regression has been evidenced mostly in randomized clinical trials with intensive lipid-lowering therapy. We aimed to demonstrate vulnerability regression in real life, with a comprehensive quantitative method, in patients with asymptomatic mild to moderate carotid atherosclerosis on a secondary prevention program. Methods and Results We conducted a single-center prospective observational study (MAGNETIC [Magnetic Resonance Imaging as a Gold Standard for Noninvasive Evaluation of Atherosclerotic Involvement of Carotid Arteries]): 260 patients enrolled at a cardiac rehabilitation center were followed for 3 years with serial magnetic resonance imaging. Per section cutoffs (95th/5th percentiles) were derived from a sample of 20 consecutive magnetic resonance imaging scans: (1) lipid-rich necrotic core: 26% of vessel wall area; (2) intraplaque hemorrhage: 12% of vessel wall area; and (3) fibrous cap: (a) minimum thickness: 0.06 mm, (b) mean thickness: 0.4 mm, (c) projection length: 11 mm. Patients with baseline magnetic resonance imaging of adequate quality (n=247) were classified as high (n=63, 26%), intermediate (n=65, 26%), or low risk (n=119, 48%), if vulnerability criteria were fulfilled in ≥2 contiguous sections, in 1 or multiple noncontiguous sections, or in any section, respectively. Among high-risk patients, a conversion to any lower-risk status was found in 11 (17%; P=0.614) at 6 months, in 16 (25%; P=0.197) at 1 year, and in 19 (30%; P=0.009) at 3 years. Among patients showing any degree of carotid plaque vulnerability, 21 (16%; P=0.014) were diagnosed at low risk at 3 years. Conclusions This study demonstrates with a quantitative approach that vulnerability regression is common in real life. A secondary prevention program can promote vulnerability regression in asymptomatic patients in the mid to long term.

Assessment of the use potential of edible sea urchins (Paracentrotus lividus) processing waste within the agricultural system: influence on soil chemical and biological properties and bean (Phaseolus vulgaris) and wheat (Triticum vulgare) growth in an amended acidic soil.

In this study we evaluated the influence of ground purple sea urchin (Paracentrotus lividus) endoskeletons, a processing waste common to all edible sea urchin plants, on the chemical, biochemical and microbiological features of an acidic (pH 5.65) sandy-loam soil. The purple sea urchin endoskeletons were characterized by a high content of total carbonates (∼94%), a moderately alkaline pH in water (pH 7.88) and electrical conductivity values (3.55 mS/cm) very similar to those of commercial lime. To evaluate the influence of the P. lividus endoskeletons on soil properties four different amendment rates were tested, notably 0.5, 1.0, 3.0 and 5.0% based on soil dry weight, and the effects compared with those recorded on unamended control soil. The addition of the purple sea urchin processing waste caused an immediate and significant pH increase which was positively related to the rate of the amendment addition. After a six months equilibration period, the differences in soil pH were still evident and significant increases of electrical conductivity and available phosphorus were also detected in soils with the higher amendment rates. The number of heterotrophic and cellulolytic bacteria and actinomycetes significantly increased after amendment addition while the number of culturable fungi steadily declined. The analysis of the Biolog Community Level Physiological Profile indicated a clear influence of the purple sea urchin processing waste on the structure of the native microbial community while a significant increase of microbial functionality (i.e. dehydrogenase activity) was recorded in soil treated with the higher amendment rates (i.e. 3.0 and 5.0%). The improvement of microbial abundance and functionality as well as the change of the microbial community structure were ascribed to the pH shift induced by the P. lividus processing waste. To investigate possible effects on soil fertility, dwarf bean (Phaseolus vulgaris) and wheat (Triticum vulgare) growth were also assessed in a pot experiment. Plant growth was unaffected (wheat) or stimulated (bean) by the amendment addition in the 0.5-3.0% range while the higher amendment rate (i.e. 5.0%) was detrimental for both plant species indicating a phytotoxic effect which could be due to different factors such as an excess of calcium in soil, a suppression of Mg uptake or the higher EC values detected at the highest amendment rate. It is concluded that ground P. lividus endoskeletons have potential as a soil amendment to ameliorate chemical and biological properties of acidic Mediterranean soils. This seems particularly relevant, especially at the lower amendment rates, since for the first time, a sustainable management system is proposed for P. lividus processing waste, which foresees economic value in the sea urchin by-product through its re-use within the agricultural production system.

Intrapartum use of zidovudine in a large cohort of pregnant women living with HIV in Italy.

BACKGROUND: Intravenous administration of zidovudine (ZDV) during labour is a key step for vertical HIV transmission (VT) prevention, but there is no evidence of benefit when maternal HIV-RNA at delivery is <50 copies/mL. The aim of this study is evaluating the appropriateness of intrapartum ZDV use in Italy. METHODS: Observational study including mother-infant pairs with perinatal HIV exposure during 2002-2019, enrolled in the Italian Register for HIV Infection in Children. Univariable and multivariable logistic regression were used to evaluate factors associated with VT. RESULTS: A total of 3,861 infants, born from 3,791 pregnancies were included. The frequency of ZDV use was 79.9%, 92.1%, 93.7% and 92.8% when HIV-RNA was not available, ≥400 copies, between 50 and 399 copies, and <50 copies/mL. Thirty-three out of 3861 (0.85%) infants were subsequently diagnosed with HIV, 25/3861 (0.6%) of them born to mothers receiving intrapartum ZDV, and 31 (93.9%) to mothers with HIV-RNA ≥50 copies/mL or not available. In women with HIV-RNA < 50 copies/mL, ART discontinuation during pregnancy was the strongest risk factor for VT (odds ratio, OR, 23.1, 95%CI 2.4-219.3), while a higher gestational age (OR 0.6, 95%CI 0.4-0.8) and PEP administration to the newborn (aOR 0.004, 95%CI <0.0001-0.4) were protective factors. Intrapartum ZDV administration did not influence the final outcome in this group. CONCLUSIONS: In ART era, more transmission events may occur in utero, limiting value of intrapartum ZDV, particularly for women with suppressed HIV-RNA load. More attention to the HIV-RNA testing of mothers before delivery may avoid unnecessary ZDV use.

The Impact of Cardiac Rehabilitation on Activities of Daily Life in Elderly Patients With Heart Failure.

Background: In elderly chronic heart failure (HF) patients, activities of daily living (ADLs) require the use of a high proportion of patients' peak aerobic capacity, heart rate, and ventilation. Objectives: To assess the effects of short-term comprehensive cardiac rehabilitation (CR) on the metabolic requirement of ADLs in elderly patients with chronic HF. Methods: The study population comprised 99 elderly chronic HF patients (mean age 72 ± 5 years, 80% male, 61% ejection fraction <40%, mean NT-proBNP 2,559 ± 4,511 pg/ml) participating in a short-term (mean days 19 ± 7) residential CR program. Before and after CR, participants, while wearing a portable ergospirometer, performed a standardized ADL battery: ADL1 (getting dressed), ADL2 (folding 8 towels), ADL3 (putting away 6 bottles), ADL4 (making a bed), ADL5 (sweeping the floor for 4 min), ADL6 (climbing 1 flight of stairs carrying a 1.5 Kg load), and ADL7 (a standard 6-min walking test). Results: After CR, task-related oxygen uptake did not change in any of the domestic ADLs. Notably, there was a significant decrease in the cumulative time required to perform ADLs (ADL 1-4 and ADL6; from 412 ± 147 to 388 ± 141 s, p = 0.001) and a reduction in maximal heart rate in ADL1 and 3 (p = 0.005 and p = 0.027, respectively). Changes occurred in the 6MWT with an increase in oxygen uptake (p = 0.005) and in the distance covered (p < 0.001) and a significant decrease in the Borg scale of dyspnea (p = 0.004). Conclusion: Elderly patients with chronic heart failure who are engaged in a short-term residential CR program improve the performance of routine ADLs.

Real-World Analysis of Survival and Clinical Events in a Cohort of Italian Perinatally HIV-1 Infected Children From 2001 to 2018.

Background: Combined antiretroviral therapy (cART) has been associated with a steep decrease in mortality and morbidity in HIV-1 infected children. New antiretroviral molecules and drug classes have been developed and the management of HIV-infected children has improved, but recent data on survival are limited. Methods: An observational retrospective study investigating changes in mortality and morbidity was conducted on 1,091 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results: Three hundred and fifty-four (32%) AIDS events and 26 (2%) deaths occurred overtime. Mortality rates decreased from 0.4/100 person-years in 2001-2006 to 0.27/100 person-years in 2007-2012 and 0.07/100 person-years in 2013-2018. Notably, 92% of the dead children were born in Italy, but only 50% were followed-up since birth or within three months of age. Seventy three percent of children had started cART at age ≥6 months; 23% were treated for <30 days before death. B and C clinical events progressively decreased (P < 0.0001). Opportunistic infections significantly decreased over time, but still were the most common events in all the periods (6.76/100 person-years in 2013-2018). In the last period, severe bacterial infections were the most common ones. Cancer rates were 0.07/100; 0.17/100; 0.07/100 person-years in the three periods, respectively. Conclusions: Progressive reductions both in mortality and in rates of class B and C clinical events and OIs have been observed during the cART era. However, deaths were still registered; more than half of dead children were enrolled after birth and had belatedly started cART.

Delphi consensus recommendations on how to provide cardiovascular rehabilitation in the COVID-19 era.

This Delphi consensus by 28 experts from the European Association of Preventive Cardiology (EAPC) provides initial recommendations on how cardiovascular rehabilitation (CR) facilities should modulate their activities in view of the ongoing coronavirus disease 2019 (COVID-19) pandemic. A total number of 150 statements were selected and graded by Likert scale [from -5 (strongly disagree) to +5 (strongly agree)], starting from six open-ended questions on (i) referral criteria, (ii) optimal timing and setting, (iii) core components, (iv) structure-based metrics, (v) process-based metrics, and (vi) quality indicators. Consensus was reached on 58 (39%) statements, 48 'for' and 10 'against' respectively, mainly in the field of referral, core components, and structure of CR activities, in a comprehensive way suitable for managing cardiac COVID-19 patients. Panelists oriented consensus towards maintaining usual activities on traditional patient groups referred to CR, without significant downgrading of intervention in case of COVID-19 as a comorbidity. Moreover, it has been suggested to consider COVID-19 patients as a referral group to CR per se when the viral disease is complicated by acute cardiovascular (CV) events; in these patients, the potential development of COVID-related CV sequelae, as well as of pulmonary arterial hypertension, needs to be focused. This framework might be used to orient organization and operational of CR programmes during the COVID-19 crisis.

An elderly-centered, personalized, physiotherapy program early after cardiac surgery.

BACKGROUND: Early post-surgery in-hospital rehabilitation in elderly patients should be aimed at accelerating the recovery of the highest level of functional autonomy and reducing the hospital stay. DESIGN: We designed a personalized physiotherapy program tailored to the frailty level of over-70-year-old patients soon after cardiac surgery. The aims of this study were (a) to validate our frailty-based approach for functional stratification of the patients, and (b) to assess the effect of the individualized program on independence and mobility, and compare it with our usual program. METHODS: We followed 224 consecutive patients aged 70-87 years, who followed either the personalized (n= 150) or usual (n= 74) program. All patients underwent a comprehensive physical functioning evaluation at the baseline and at the end of hospitalization. RESULTS: The frailty-based stratification was successful in identifying those patients at higher risk of falls, with heavy nursing needs, greater dependency, and poorer heath status perception. On discharge, both groups had significantly improved on all measures of independence and mobility, but most of these changes (nursing needs, mobility, balance, and muscle strength) were significantly greater (P < 0.05) in the intervention group. These patients also had a significantly shorter length of stay (17.5 ± 8 vs. 21 ± 4 days, P = 0.0002), and 91% of them could be discharged in a state of substantial independence. CONCLUSION: An elderly-centered stratification based on functional frailty is useful to identify patients with more dependency and greater needs. A consequent personalized physiotherapy program designed to enhance independent mobility soon after cardiac surgery is safe and well accepted, and is more effective then usual physiotherapy.

Serological screening for hepatitis C during pregnancy: Seroprevalence and maternal and neonatal outcomes in 45,000 pregnant women.

OBJECTIVES: The study evaluates the trend over time and the results of serological screening for hepatitis C infection in pregnancy and obstetric and neonatal outcomes. STUDY DESIGN: It is a retrospective observational study of all pregnant women delivered in maternity units in Trento province, North East Italy, between 2009-2018. Serological screening data for hepatitis C virus were collected through the birth attendance certificate that is the mandatory tool in Italy for the birth report and the monitoring of the pregnancy, childbirth and health of the newborn. We also used the informations collected in the Hospital information system in order to get, for confirmed positive cases, the data of the entire serological profile. On this basis, we calculated the coverage of serological screening, the seroprevalence of the infection and the obstetric and neonatal outcomes. RESULTS: A total of 45,493 pregnant women were analysed, 75.5% Italians and 24.5% foreigners. The mean coverage for serological HCV screening in pregnancy was 99.4%. 177 women tested positive for HCV antibodies (107 Italian and 70 foreign women). Mean overall seroprevalence in pregnant women was 3.9‰ (95% CI: 3.8-4.0); amongst Italians it was 3.2‰ (95% CI: 3.0-3.4) and amongst foreigners it was 6.1‰ (95% CI: 5.9-6.2). The highest seroprevalence was recorded in mothers coming from Asian countries. HCV positive mothers present an excess risk for intrahepatic cholestasis and gestational diabetes compared to HCV negative mothers. The neonatal outcomes considered bring to light a statistically significant increase in preterm births, low birth weight, elective Caesarean births, hospitalisation at birth and bottle- or mixed-feeding vs breast-only feeding. There are differences in obstetric and neonatal outcomes in relation to the HCV positive subgroup of the mother defined in particular by exposure to smoke and/or opioids. CONCLUSIONS: The availability and integration of current information sources allows you to verify compliance with national recommendations on the serological screening of hepatitis C virus infection, to determine infection seroprevalence, the characteristics of the cases and the obstetric and neonatal outcomes. Only part of the maternal and neonatal outcomes studied can be attributed to the presence of HCV.

Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy.

BACKGROUND: Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking. METHODS: We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]:4.21-7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided. RESULTS: Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71-5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4+ T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4+ T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001). CONCLUSION: Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed.

Diagnosis of paroxysmal atrial fibrillation in patients with implanted pacemakers: relationship to symptoms and other variables.

BACKGROUND: Atrial fibrillation (AF) is not always accompanied by clear-cut symptoms and symptoms suggestive of AF may not correspond to a genuine AF episode. The study prospectively evaluated the burden of asymptomatic AF episodes in pacemaker patients (for sick sinus syndrome) with a history of documented paroxysmal AF. METHODS: Consecutive patients were enrolled and implanted with dual-chamber pacemakers equipped with diagnostic features for AF monitoring. Each patient was instructed about typical AF symptoms and was asked to keep a detailed log of symptoms. Stored pacemaker data were analyzed using only AF episodes >30 s. RESULTS: The mean follow-up was 16 +/- 6 months and 102 patients were enrolled (73 +/- 7 years, 59 M). Thirteen patients (13%) dropped out with the development of permanent AF and their data were discarded. Twenty-three patients (26%) without device-stored AF episodes all reported at least one annotated AF episode. There were 1,245 device-stored AF episodes in 66 (74%) out of 89 patients. Patients reported 1,141 episodes of AF-related symptoms. Only 240 (21%) corresponded to a genuine device-stored AF event. The sensitivity and positive predictive value of symptoms to detect AF were respectively 19% and 21%. Episode duration, rate increase at the onset of the arrhythmia, heart disease, or antiarrhythmic drug therapy showed no statistically significant differences comparing symptomatic and asymptomatic episodes. CONCLUSIONS: Many pacemaker patients with paroxysmal AF can develop AF-like symptoms in the absence of device-stored AF. AF-related symptoms have low sensitivity and low positive predictive value in patients with permanent pacemakers.