Extrapulmonary and Drug-Resistant Childhood Tuberculosis: Unveiling the Disease to Adopt the Optimal Treatment Strategy.

Paediatric tuberculosis (TB) is a substantial threat among infectious diseases, particularly considering the high risk of extrapulmonary tuberculosis (EPTB), severe forms of the disease, and the spreading of drug-resistant strains. Describing the characteristics of children with EPTB and those with drug-resistant tuberculosis (DR-TB) and analysing the role of second-line drugs could facilitate the management of these cases. This retrospective study was conducted on 271 children diagnosed with active TB disease (44 EPTB cases, 9 DR-TB cases), originating from diverse geographic areas, who were referred to the infectious disease unit at Meyer Children's Hospital, Florence, Italy, from 2006 to 2022. In most patients, the management of therapies was complicated by the impossibility to obtain drug susceptibility testing (DST) results, which improved over the years: 17/154 (11.04%) children had DST results between 2006 and 2013, and 50/117 (42.73%, p < 0.001) between 2014 and 2022. Second-line drugs were not exclusively administered to DR-TB cases, but also to EPTB cases (20/44, 45.45%). Drugs were generally well tolerated; adverse events occurred in 13 children (13/271, 4.80%) and were generally mild and reversable. Therapies were successful in 267 children (98.52%) considered cured, while 4 (1.48%) presented sequelae. Both univariate and multivariate logistic regression analyses were conducted to investigate factors associated with EPTB, DR-TB, and second-line drugs administration. Originating from Asia emerged as a risk factor associated with both EPTB and DR-TB (p = 0.013 and p = 0.045, respectively). The introduction of GeneXpert tests has significantly improved TB diagnosis and the obtaining of DST results. The administration of second-line therapies should be limited primarily to DR-TB cases, but it is possible that these drugs may also be beneficial in selected EPTB cases.

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.

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.

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.

Characteristics, Management and Outcomes of Spondylodiscitis in Children: A Systematic Review.

Spondylodiscitis (SD) is the concurrent infection of the intervertebral disc and the adjacent vertebral bodies. Currently, there is a substantial lack of structured reviews about this topic. The aim of this study was to systematically review the available literature in order to determine the main features of pediatric SD. A systematic search of MEDLINE database was performed, according to the PRISMA guideline recommendations. Clinical features, laboratory data, radiological signs, treatments strategies, and outcomes were summarized. Studies' quality assessments were performed using the JBI Critical Appraisal Checklists. A total of 35 retrospective studies were analyzed and 340 children were identified. The most frequently affected age class was 0.5-4 years. The most affected site was the lumbar spine. The most commonly reported symptoms were back pain (37.97%) and refusal to walk/to stand/to sit (49.79%). The most frequently identified pathogen was Staphylococcus aureus (n = 33). The most used antibiotics were third generation cephalosporins. The intravenous therapy duration range was 1-25 weeks, the oral therapy duration range was 5 days-36 months. Surgery was used in 5.88% of children. In 29 cases clinical sequelae were documented. This study provides the main features of pediatric SD; it also emphasizes the significant gaps in the literature regarding this topic.

Use of Second-line Medications and Treatment Outcomes in Children With Tuberculosis in a Single Center From 2007 to 2018.

BACKGROUND: The incidence of drug-resistant forms of tuberculosis (DR-TB) and the number of children treated with second-line drugs (SLDs) are increasing. However, limited amount of information is available regarding the use of SLDs in this population. METHODS: To describe the treatment of pediatric TB with SLDs and factors associated with use of SLDs in children with and without documented DR-TB, records of pediatric TB patients referred to a center in Italy from 2007 to 2018 were reviewed retrospectively. RESULTS: Of 204 children diagnosed with active TB during the study period, 42 were treated with SLDs because of confirmed or probable drug resistance (42.8%), adverse reactions to first-line drugs (7.1%), central nervous system involvement (11.9%) or unconfirmed possible drug resistance (38.1%). There were no deaths or adverse reactions to SLDs reported. Treatment was successful in 85.2% children treated with first-line drugs and 92.9% children treated with SLDs. After adjusting for calendar period, the only factor associated with DR-TB was <2 years old [odds ratio (OR): 5.24 for <2 years vs. 5-18 years; P = 0.008]. Factors associated with treatment with SLDs were TB at 2 or more sites (OR: 11.30; P < 0.001), extrapulmonary TB (OR: 8.48; P < 0.001) or adverse reactions to first-line drugs (OR: 7.48; P = 0.002). No differences were noted in age or region of origin. CONCLUSIONS: A substantial proportion of TB children were treated with SLDs. The main reason for using SLDs was failure of a first-line drug regimen, suggesting possible DR-TB and underestimation of DR-TB in children. The use of SLD regimens was associated with a high success rate and good tolerability profile.

Accuracy of presepsin in neonatal sepsis: systematic review and meta-analysis.

INTRODUCTION: Neonatal sepsis represents a major cause of morbidity and mortality in neonates. No diagnostic test has been demonstrated to be sufficiently accurate to confirm or exclude neonatal sepsis. This study aimed to evaluate the diagnostic accuracy of presepsin (P-SEP) for neonatal sepsis. Areas covered: A systematic review of literature was performed on Medline and EMBASE. A meta-analysis was performed to calculate pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic of P-SEP for neonatal sepsis. Eight studies were included, involving 636 neonates. Pooled sensitivity and specificity were 0.90 and 0.90, respectively. The pooled DOR was 120.94, and the Area Under Curve (AUC) was 0.968, indicating a high level of diagnostic accuracy. Using cut-off values <600 ng/L, sensitivity reached 0.93, with a specificity of 0.81 and AUC 0.8195, while using a threshold >600 ng/L, sensitivity was 0.87 and specificity 0.97, with higher diagnostic accuracy (AUC 0.976). Significant heterogeneity was found between studies. Expert commentary: Diagnostic accuracy of P-SEP resulted high in detecting neonatal sepsis. Even though it cannot be recommended as a single diagnostic test, P-SEP could be a helpful and valuable biomarker in neonates with suspected sepsis.

Strategies for Prevention of Mother-to-Child Transmission Adopted in the "Real-World" Setting: Data From the Italian Register for HIV-1 Infection in Children.

BACKGROUND: Strategies for prevention of HIV-1 mother-to-child transmission (PMTCT) have been continuously optimized. However, cases of vertical transmission continue to occur in high-income countries. OBJECTIVES: To investigate changes in PMTCT strategies adopted by Italian clinicians over time and to evaluate risk factors for transmission. METHODS: Data from mother-child pairs prospectively collected by the Italian Register, born in Italy in 1996-2016, were analyzed. Risk factors for MTCT were explored by logistic regression analyses. RESULTS: Six thousand five hundred three children (348 infections) were included. In our cohort, the proportion of children born to foreign mothers increased from 18.3% (563/3078) in 1996%-2003% to 66.2% (559/857) in 2011-2016 (P < 0.0001). Combination neonatal prophylaxis use significantly (P < 0.0001) increased over time, reaching 6.3% (56/857) after 2010, and it was largely (4.2%) adopted in early preterm infants. The proportion of vaginal deliveries in women with undetectable viral load (VL) increased over time and was 9.9% (85/857) in 2011-2016; no infection occurred among them. In children followed up since birth MTCT, rate was 3.5% (96/2783) in 1996-2003; 1.4% (36/2480) in 2004-2010; and 1.1% (9/835) in 2011-2016. At a multivariate analysis, factors associated with MTCT were vaginal delivery with detectable or missing VL or nonelective caesarean delivery, prematurity, breastfeeding, lack of maternal or neonatal antiretroviral therapy, detectable maternal VL, and age at first observation. Previously described increased risk of offspring of immigrant women was not confirmed. CONCLUSIONS: Risk of MTCT in Italy is ongoing, even in recent years, underling the need for implementation of the current screening program in pregnancy. Large combination neonatal prophylaxis use in preterm infants was observed, even if data on safety and efficacy in prematures are poor.

Procalcitonin performance in detecting serious and invasive bacterial infections in children with fever without apparent source: a systematic review and meta-analysis.

INTRODUCTION: The management of children with fever without apparent sources (FWAS) is difficult. This study aimed to evaluate the diagnostic accuracy of procalcitonin (PCT) in detecting serious or invasive bacterial infection (SBI or IBI) in children with FWAS. Areas covered: A systematic review of literature from 2007 to 2017 was performed on Medline. Twelve studies were included, involving 7,260 children with FWAS and analyzing the diagnostic performance of PCT. Four meta-analyses were performed to calculate pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve for PCT in detecting SBI and IBI, at two different thresholds. Considering IBI, PCT sensitivity and specificity at a threshold of 0.5 ng/mL were 0.82 and 0.86, respectively; at a threshold of 2 ng/mL sensitivity and specificity were 0.61 and 0.94, respectively. In detecting SBI, PCT performance was lower, with 55% sensitivity and 85% specificity at a threshold of 0.5 ng/mL, and 30% sensitivity and 95% specificity at a threshold of 2 ng/mL. Expert commentary: Considering IBI, results showed high diagnostic accuracy for PCT. Conversely, PCT performance in diagnosis of SBI was poor. These findings suggest that PCT level determination could be helpful in detecting meningitis, bacteremia and sepsis in children with FWAS.

Use of combination neonatal prophylaxis for the prevention of mother-to-child transmission of HIV infection in European high-risk infants.

OBJECTIVES: To evaluate use of combination neonatal prophylaxis (CNP) in infants at high risk for mother-to-child transmission (MTCT) of HIV in Europe and investigate whether CNP is more effective in preventing MTCT than single drug neonatal prophylaxis (SNP). DESIGN: Individual patient-data meta-analysis across eight observational studies. METHODS: Factors associated with CNP receipt and with MTCT were explored by logistic regression using data from nonbreastfed infants, born between 1996 and 2010 and at high risk for MTCT. RESULTS: In 5285 mother-infant pairs, 1463 (27.7%) had no antenatal or intrapartum antiretroviral prophylaxis, 915 (17.3%) had only intrapartum prophylaxis and 2907 (55.0%) mothers had detectable delivery viral load despite receiving antenatal antiretroviral therapy. Any neonatal prophylaxis was administered to 4623 (87.5%) infants altogether; 1105 (23.9%) received CNP. Factors significantly associated with the receipt of CNP were later calendar birth year, no elective caesarean section, maternal CD4 cell count less than 200 cells/µl, maternal delivery viral load more than 1000 copies/ml, no antenatal antiretroviral therapy, receipt of intrapartum single-dose nevirapine and cohort. After adjustment, absence of neonatal prophylaxis was associated with higher risk of MTCT compared to neonatal prophylaxis [adjusted odds ratio (aOR) 2.29; 95% confidence interval (95% CI) 1.46-2.59; P < 0.0001]. Further, there was no association between CNP and MTCT compared to SNP (aOR 1.41; 95% CI 0.97-2.5; P = 0.07). CONCLUSION: In this European population, CNP use is increasing and associated with presence of MTCT risk factors. The finding of no observed difference in MTCT risk between one drug and CNP may reflect residual confounding or the fact that CNP may be effective only in a subgroup of infants rather than the whole population of high-risk infants.

Antiretroviral use in Italian children with perinatal HIV infection over a 14-year period.

BACKGROUND: Information on the use of new antiretroviral drugs in children in the real setting of clinical fields is largely unknown. METHODS: Data from 2554 combined antiretroviral therapy (cART) regimens administered to 911 children enrolled in the Italian Register for HIV infection in children, between 1996 and 2009, were analysed. Factors potentially associated with undetectable viral load and immunological response to cART were explored by Cox regression analysis. RESULTS: Proportion of protease inhibitor (PI)-based regimens significantly decreased from 88.0% to 51.2% and 54.9%, while proportion on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens increased from 4.5% to 38.8% and 40.2% in 1996-1999, 2000-2004 and 2005-2009, respectively (p < 0.0001). Significant change in the use of each antiretroviral drug occurred over the time periods (p < 0.0001). Factors independently associated with virological and immunological success were as follows: later calendar periods, younger age at regimen (only for virological success) and higher CD4(+) T-lymphocyte percentage at baseline. Use of unboosted PI was associated with lower adjusted hazard ratio (aHR) of virological or immunological success with respect to NNRTI- and boosted PI-based regimens, with no difference among these two latter types. CONCLUSION: Use of new generation antiretroviral drugs in Italian HIV-infected children is increasing. No different viro-immunological outcomes between NNRTI- and boosted PI-based cART were observed.

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.

Changing patterns of clinical events in perinatally HIV-1-infected children during the era of HAART.

BACKGROUND: The introduction of HAART has decreased mortality and progression to AIDS in perinatally HIV-1-infected children, but information on modification of the rate of specific clinical events is limited. METHOD: An observational population study on changes in HIV-1-related morbidity was conducted on 1402 perinatally HIV-1-infected children enrolled in the Italian Register for HIV Infection in Children and prospectively followed in the pre-HAART (1985-1995) and post-HAART periods (1996-2000, and 2001-2005). Of this group, 773 children (55.1%) were followed from birth. Median observation time was 8.58 years (interquartile range, 3.71-13.72). RESULTS: Overall, 666 (47.5%) children developed AIDS and 420 (29.9%) died. Improved survival over time was evidenced at Kaplan-Meier analysis (P < 0.0001). Poisson regression analysis indicated that Centers for Disease Control and Prevention class B and C clinical event rates and most of the HIV-1-related organ complication rates significantly decreased starting from 1996-2000. Significant reductions in rates of cancer and opportunistic infections were evidenced after 2000. Nevertheless, opportunistic infections still occurred at high rates (6.09/100 person-years) in 2001-2005, with high rate of bacterial infections (3.55/100 person-years), particularly pneumonia (1.66/100 person-years), in this period. CD4 cell percentage was > 15% in 58.5% children with pneumonia. CONCLUSIONS: Progressive reductions of both mortality and rates of class B and C clinical events, including organ complications, were evidenced in the HAART era. Nevertheless, severe bacterial infections, particularly pneumonia, still occurred at considerable high rates, even in the absence of a severe CD4 cell depletion.

Cancer rates after year 2000 significantly decrease in children with perinatal HIV infection: a study by the Italian Register for HIV Infection in Children.

PURPOSE: To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. PATIENTS AND METHODS: An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. RESULTS: Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). CONCLUSION: Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.

[Determinants of occupational injuries in the construction of the "high speed train" Bologna-Florence]. / I determinanti degli infortuni sul lavoro nella costruzione della linea ferroviaria "treno ad alta velocità" Bologna-Firenze.

OBJECTIVE: to study determinants of occupational injuries in tunnel construction using data from the surveillance system which had been implemented in order to monitor accidents during the construction of the "high speed train tracks in the Italian Regions Emilia-Romagna and Tuscany. DESIGN: retrospective cohort study. SETTING: 16 sites for the construction of 14 tunnels of the high speed railway-tract Bologna-Firenze, in Italy. PARTICIPANTS: 1,602 workers (of 3,000 employed in the underground tunnelling), aged 18 - 67 years, operating during excavation with traditional method in 1999-2002. A total of 549 injuries occurred among 385 workers. The number of worked hours were used as time at risk. MAIN OUTCOME MEASURES: incidence rate ratios (IRR) and 95% confidence intervals for all injuries, serious injuries and first injuries were considered in separate multiple regression analyses (Poisson). RESULTS: residence, task and working phase were taken into consideration. An increased risk was found for younger workers, for carpenters (IRR "all-events" = 2.33; 95% CI=1.85-2.94; IRR" first-events" = 2.12; 95% CI 1.62-2.77) and miners (IRR "all-events" = 1.76; 95% CI 1.39-2.24; IRR"first-events" = 1.71; 95% CI 1.30-2.24) vs. machinery operators. Construction of inverted arch turns out to have an incidence rate ratio three times higher than digging out (IRR "all-events" = 2.79; 95% CI 2.27-3.43; IRR "firsts-event = 2.98; 95% CI 2.33-3.81). The probability of "serious" injuries (>30 days) is higher for miners (IRR=2.45; 95% CI 1.65-3.64) and for carpenters (IRR=2.31; 95% CI 1.53-3.49). CONCLUSION: this study pointed out to indicate some determinants (age, task and work phase) of injuries in tunneling about which little had been published previously. These results are useful for addressing preventive measures, for control and prevention activities and point to the need to explore the effect of experience and to study, through a case crossover design, transient working and individual risk factors for traumatic injury within these working sites.

Virologic, immunologic, and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection.

OBJECTIVE: To investigate the impact of early versus deferred combined antiretroviral treatment (ART) in asymptomatic or moderately symptomatic [Centers for Disease Control and Prevention (CDC) category N, A or B] infants with perinatal HIV-1 infection. METHODS: A multi-centre nationwide case-control study was conducted. Data from 30 infants treated with combined ART with three or more drugs before 6 months of age were compared with data from 103 infants starting ART with three or more drugs after 6 months of age. The median follow-up time was 4.1 years (range, 1.0-6.5 years). RESULTS: No difference was evident in the first available viral load and CD4 T-lymphocyte percentage between the two groups of children. Early-treated infants showed significantly lower viral loads than infants receiving deferred treatment at all the follow-up periods. A higher proportion of early-treated infants than infants receiving deferred treatment (73.3% versus 30.1%; P < 0.0001) reached an undetectable viral load. Higher CD4 T-lymphocyte percentages were found in early-treated infants at 13-24 (P < 0.0001), 25-36 (P < 0.0001), and 37-48 (P = 0.003) months of age. No early-treated infant versus 20 of 103 (19.4%) infants receiving deferred ART (P = 0.02) showed a CD4 T-lymphocyte percentage of less than 15% at one time point during follow-up. No CDC category A, B or C clinical event occurred in early-treated infants over the follow-up period while 44 of 103 (42.7%) infants receiving deferred treatment presented a decline in the CDC category. Kaplan-Meier analyses revealed significant differences in CDC category A (P = 0.0002), B (P = 0.0003), and C (P = 0.0018) event-free survivals. CONCLUSION: The data suggest virologic, immunologic, and clinical benefits from early administration of ART.

[Experience of epidemiological surveillance of reproductive health in women employed in the health field]. / Sperimentazione di un sistema di sorveglianza epidemiologica per la salute riproduttiva di donne che lavorano nel comparto ospedaliero.

Aim of this paper is to describe the methodology adopted to build up an epidemiological surveillance system on the reproductive health of women employed by the Regional Health System (Hospital Division). The implementation of this system required the set up of a relational database, with personal and health data collected from the 1st January 1998 to the 31st December 1998. The goals of research were: to describe the phenomenon of unfavorable reproductive events such as: death at birth, low weight at birth, birth defects, spontaneous abortions, voluntary abortions (for reasons linked to the child's and the pregnant woman's health), premature births and post term births; to provide the basis for further analytical studies on working activities with exposures of particular interest (antiblastic drugs, ionizing radiations and ergonomic factors); to contribute to evaluate the state of enforcement of the specific legislation. We computed raw, age-specific and standardized rates of the studied population as far as natality, spontaneous and voluntary abortivity and birth defects are concerned. The results showed an increased number of spontaneous abortions. Investigations are still in progress and an estimate of risks associated with chemical and physical exposures in this sector will be determined.