Characteristics of nursing homes and early preventive measures associated with risk of infection from COVID-19 in Lazio region, Italy: a retrospective case-control study.

OBJECTIVES: To understand which organisational-structural characteristics of nursing homes-also referred to as long-term care facilities (LTCFs)-and the preventative measures adopted in response to the pandemic are associated with the risk of a COVID-19 outbreak. SETTING: LTCFs in Lazio region in Italy. DESIGN: The study adopts a case-control design. PARTICIPANTS: We included 141 facilities and 100 provided information for the study. Cases were defined as facilities reporting a COVID-19 outbreak (two or more cases) in March-December 2020; controls were defined as LTCFs reporting one case or zero. The exposures include the structural-organisational characteristics of the LTCFs as reported by the facilities, preventative measures employed and relevant external factors. RESULTS: Twenty facilities reported an outbreak of COVID-19. In binary logistic regression models, facilities with more than 15 beds were five times more likely to experience an outbreak than facilities with less than 15 beds OR=5.60 (CI 1.61 to 25.12; p value 0.002); admitting new residents to facilities was associated with a substantially higher risk of an outbreak: 6.46 (CI 1.58 to 27.58, p value 0.004). In a multivariable analysis, facility size was the only variable that was significantly associated with a COVID-19 outbreak OR= 5.37 (CI 1.58 to 22.8; p value 0.012) for larger facilities (>15 beds) versus smaller (<15 beds). Other characteristics and measures were not associated with an outbreak. CONCLUSION: There was evidence of a higher risk of COVID-19 in larger facilities and when new patients were admitted during the pandemic. All other structural-organisational characteristics and preventative measures were not associated with an outbreak. This finding calls into question existing policies, especially where there is a risk of harm to residents. One such example is the restriction of visitor access to facilities, resulting in the social isolation of residents.

The Effectiveness of Intervening on Social Isolation to Reduce Mortality during Heat Waves in Aged Population: A Retrospective Ecological Study.

BACKGROUND: Heat waves are correlated with increased mortality in the aged population. Social isolation is known as a vulnerability factor. This study aims at evaluating the correlation between an intervention to reduce social isolation and the increase in mortality in the population over 80 during heat waves. METHODS: This study adopted a retrospective ecologic design. We compared the excess mortality rate (EMR) in the over-80 population during heat waves in urban areas of Rome (Italy) where a program to reduce social isolation was implemented, to others where it was not implemented. We measured the mortality of the summer periods from 2015 to 2019 compared with 2014 (a year without heat waves). Winter mortality, cadastral income, and the proportion of people over 90 were included in the multivariate Poisson regression. RESULTS: The EMR in the intervention and controls was 2.70% and 3.81%, respectively. The rate ratio was 0.70 (c.i. 0.54-0.92, p-value 0.01). The incidence rate ratio (IRR) of the interventions, with respect to the controls, was 0.76 (c.i. 0.59-0.98). After adjusting for other variables, the IRR was 0.44 (c.i. 0.32-0.60). CONCLUSIONS: Reducing social isolation could limit the impact of heat waves on the mortality of the elderly population.

Seasonal influenza vaccination among health-care workers: the impact of different tailored programs in four University hospitals in Rome.

Seasonal influenza vaccination (SIV) of health-care workers (HCWs) is recommended in most countries to protect them and their patients from infection. Although SIV can reduce the risk of influenza complications among vulnerable patients, vaccination uptake is generally unsatisfactory. The present study aimed to assess the impact of different programs in promoting SIV uptake among HCWs during the season 2017/2018 in four teaching hospitals in Rome. A multicentric cross-sectional study was carried out, in order to describe the four different campaigns and to assess their impact by identifying and developing a set of indicators that provide information about the vaccination services, the percentage of invited HCWs, the vaccinators' workforce and the vaccination coverage rates.The hospitals organized different strategies: Hospital 1, 3 and 4 organized educational courses for HCWs and actively invited every single HCW through e-mail. All the hospitals organized a dedicated unit for influenza vaccination, and Hospital 1 added on-site vaccination sessions that required a large number of staff. Hospital 1 and hospital 4 registered a comparable vaccination coverage rate, 12.97% and 12.76%, respectively, while it was 6.88% in Hospital 2 and 4.23% in Hospital 3. Our indicators demonstrated to be effective and useful for analyzing the different SIV campaigns. The results suggest that the best practice to promote SIV among HCWs should include multiple approaches. Among those, an easy access to the vaccination site seems to play a key role in determining a higher vaccination coverage.

Plasma levels of CRP, neopterin and IP-10 in HIV-infected individuals with and without pulmonary tuberculosis.

INTRODUCTION: Tuberculosis (TB) is a major cause of morbidity and death worldwide, and disproportionally affects people with HIV. Many cases still remain undiagnosed, and rapid and effective screening strategies are needed to control the TB epidemics. Immunological biomarkers may contribute. METHODS: Plasma samples from healthy individuals (n: 12) and from HIV-infected individuals with (n: 21) and without pulmonary TB (n: 122) were tested for C-reactive protein (CRP), neopterin, and interferon-gamma-inducible protein-10 (IP-10). Increased levels of biomarkers and WHO 4-symptom-screening were compared with the presence of pulmonary TB. Survival status at 12 months was recorded. Associations with CD4 count, BMI, haemoglobin, disease severity, and mortality were analysed. RESULTS: The plasma levels of the biomarkers were significantly higher in TB-positive (n:21) compared to TB-negative (n:122) subjects. WHO symptoms, increased neopterin (>10 nmol/L) and CRP (>10 mg/L) showed similar sensitivity and different specificity, with increased CRP showing higher and increased neopterin lower specificity. The three markers were inversely correlated to haemoglobin and to CD4, and CRP levels inversely correlated to BMI. The markers were also significantly higher in individuals with subsequent mortality and in individuals with higher mycobacterial load in sputum according to Xpert results (IP-10 and CRP). CONCLUSION: This study showed significant associations of the biomarkers analysed with TB infection and mortality, that could have potential clinical relevance. Biomarker levels may be included in operational research on TB screening and diagnosis.

Noncommunicable Diseases Burden and Risk Factors in a Cohort of HIV+ Elderly Patients in Malawi.

HIV-infected patients have increased risk of noncommunicable diseases (NCDs). HIV+ patients in Africa are experiencing growing comorbidities due to increase in life expectancy and long-time antiretroviral therapy (ART). HIV prevalence in Malawi is one of highest in the world (10.8% in women and 6.4% in men); few data are available about NCDs epidemiology in HIV+ elderly patients in Malawi. A retrospective analysis of routine medical records in 14 health centers run by Disease Relief through Excellent and Advanced Means (DREAM) program in Malawi was carried out. All HIV+ patients aged >40 years in care in the period January 01, 2017-December 31, 2018 were included. Clinical and laboratory features were collected in the last visit of the study period. Files from 7,071 patients (62.1% women) in ART were analyzed, 362 (5.1%) were aged >65 years. Median time on ART was 98.9 (64.8-118.0) months; median body mass index, haemoglobin (HB), and CD4 count were, respectively, 21.63 kg/m2 (19.5-24.5), 13 mg/dL (12-14), and 457 cell/mm3 (328-613). Elderly patients >65 years were more likely to be malnourished (odds ratio [OR] = 2.0, confidence interval [CI]: 1.54-2.59), diagnosed with arterial hypertension (OR = 2.5, CI: 1.94-3.43), affected with diabetes (OR = 2.7, CI: 1.25-6.22), have macrocytic anemia (OR = 2.5, CI: 2.00-3.35), and increased serum creatinine (OR = 1.5, CI: 1.03-2.43]). Other factors were associated with NCD burden, but age remained always independently related. Two concomitant chronic conditions in addition to HIV were present in 19.2% (66/343) of elderly people and 5.2% (338/6.454) of patients aged <65 years (OR = 4.3, CI: 3.22-5.76). Some associations were observed: nevirapine (NVP) was associated with kidney disease (OR = 1.5, CI: 1.22-2.06), NVP and protease inhibitor (PI) with hypertension (OR = 2.79, CI: 2.16-3.35 and OR = 2.15, CI: 1.52-3.02), azidothymidine (AZT) with macrocytic anemia (OR = 15.6, CI: 13.18-18.68). NVP, AZT, and duration of any ART >3 years were associated with the presence of two or more comorbidities (OR = 2.1 1.54-2.96, OR = 2.6 1.87-3.71, and OR = 1.7 1.12-2.84). Our data show the burden of NCDs in aging HIV+ patients in Malawi. The expansion of HIV treatment programs will require special attention to such comorbidities in elderly patients.

Cost of hospital care for the older adults according to their level of frailty. A cohort study in the Lazio region, Italy.

BACKGROUND: The increasing burden of chronic diseases associated with the ageing of the European population constitutes one of the main challenges for the welfare systems in developed western countries, especially through its impact on the use of hospital services and the cost of care. This study aims at evaluating the cost of hospital care for older adults living in the Lazio Region, Italy, according to their level of frailty. METHODS: Since 2014 a longitudinal randomized cohort study has been carried out on a sample consisting of 1280 older adults aged over 64 years resident in the Lazio region (Italy), with their being evaluated for multidimensional frailty. Accesses to Hospital Services (acute care and Day Hospital care admissions and Emergency Room accesses) during the first year after enrolment, as well as the related costs have been recorded through a regional database. Costs have been stratified on the basis of the state of frailty. RESULTS: The analysis of hospital services and costs highlights the role played by pre-frail individuals who generated 49.3% of the hospital care cumulative costs. Hospital Admission (HA) costs arising from robust and pre-frail subjects are 70% of the total HA costs. Pre-frail individuals also showed the highest average HA cost per person/year (7062.89 Euros). The main determinant of the highest HA costs was given by the number of HAs during the follow-up (multivariate linear regression, ß coefficient = 0.319; p<0.001), which was higher among pre-frail individuals than in any other group of patients. CONCLUSIONS: Pre-frail individuals generated the highest cost for hospital care in a sample of representative subjects living in an Italian Region with a low rate of community care services, as is the case in the Lazio region. Assessment of the multidimensional frailty of older adults permits a better definition of the important target of the pre-frail population as the main category within which interventions to prevent or mitigate frailty should be carried out.

Immune Activation and Microbial Translocation Markers in HIV-Exposed Uninfected Malawian Infants in the First Year of Life.

BACKGROUND: HIV-exposed uninfected (HEU) infants show a high rate of morbidity. We aimed to investigate on biomarkers of immune activation/microbial translocation in HEU infants, evaluating the impact that infections/malnutrition can have on biomarker levels during the first year of life. METHODS: Clinical data of 72 Malawian infants were recorded monthly and correlated with levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP) and intestinal fatty acid-binding protein (I-FABP), analyzed longitudinally. RESULTS: Levels of sCD14 and LBP showed a significant age-related increase. Higher levels of LBP (19.4 vs. 15.2 µg/ml) were associated with stunting, affecting 30% of the infants. The association remained statistically significant after adjusting for cytomegalovirus acquisition, malaria and respiratory infections (p = 0.031). I-FABP levels were significantly increased in infants experiencing gastrointestinal infections (1442.8 vs. 860.0 pg/ml, p = 0.018). CONCLUSION: We provide evidence that stunting is associated with an enhanced inflammatory response to microbial products in HEU children, suggesting that malnutrition status should be taken into consideration to better understand the alteration of the immune profile of HEU infants living in poor socioeconomic settings.

A multivariate genetic analysis confirms rs5010528 in the human leucocyte antigen-C locus as a significant contributor to Stevens-Johnson syndrome/toxic epidermal necrolysis susceptibility in a Mozambique HIV population treated with nevirapine.

Objectives: Nevirapine is used in developing countries for the treatment of HIV infection, but its use is associated with rare serious adverse reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Recently, an association between rs5010528 in the human leucocyte antigen (HLA)-C locus and SJS/TEN susceptibility has been described in sub-Saharan populations. Our aim was to verify this association in a population of nevirapine-treated patients from Mozambique. Methods: The rs5010528 SNP was analysed by direct sequencing in 27 patients who had developed SJS/TEN and 75 patients who did not develop adverse reactions after nevirapine treatment. A case-control association study was conducted. A multivariate analysis was performed in order to evaluate the role of HLA-C also in relation to other susceptibility genetic factors (CYP2B6, TRAF3IP2, HCP5, PSORS1C1 and GSTM1 genes). Results: rs5010528 was significantly associated with a higher risk of developing SJS/TEN; the variant allele was more frequent in cases than in controls, conferring a high risk of developing this adverse reaction in carriers (OR = 5.72 and P = 0.0002 at genotype level, OR = 3.51 and P = 0.0002 at allelic level). The multivariate analysis showed that the HLA-C SNP, CYP2B6 (rs28399499), TRAF3IP2 (rs76228616) and GSTM1 (null genotype) can explain 25% of the susceptibility to this reaction, with the HLA-C SNP as the most significant contributor (P = 0.02 and OR = 5.64). Conclusions: Our study confirmed the association of the rs5010528 SNP in the HLA-C region with susceptibility to developing SJS/TEN in a population from Mozambique, suggesting that it could be a good genomic biomarker for SJS/TEN susceptibility in different sub-Saharan populations.

Deficit of IgG2 in HIV-positive pregnant women is responsible of inadequate IgG2 levels in their HIV-uninfected children in Malawi.

BACKGROUND: Transplacental passage of IgGs is impaired in HIV + pregnant women, possibly determining an inadequate immunological protection in their children. We aimed to determine the impact of maternal immunological IgG profile and immunoactivation status on the efficiency of transplacental passage of IgG subclasses in HIV + mothers. METHODS: 16 mother/infants pairs were studied in Malawi. Mothers received antiretroviral therapy (ART) from the third trimester of pregnancy. Determinations of pre-ART levels of maternal sCD14, of IgG subclasses in mothers at delivery and in their 1-month-old infants, were performed using commercial ELISA kits. RESULTS: At delivery, after a median of 10 weeks of ART, 12/16 mothers were hypergammaglobulinemic, with IgG levels (20.5 mg/ml, 95% CI:18.8-26.8) directly correlated to the plasmatic levels of sCD14 (r = 0.640, p = 0.014). IgG1 levels (17.9 mg/ml) accounted for 82% of IgG, IgG3 and IgG4 levels were in the normal range. A profound deficit of IgG2 was observed both in mothers (0.60 mg/ml) and in infants (0.14 mg/ml). Placental transfer ratio (range 0.16-0.42) did not show a selective impairment between the different IgG subclasses. The transplacental passage of all IgG subclasses was decreased in the presence of maternal IgG over 16 mg/ml (significantly for IgG1, p = 0.031) and of high levels of sCD14 (p = 0.063). CONCLUSIONS: Transplacental passage was reduced for all IgG subclasses and inversely correlated to high levels of maternal IgGs and to the degree of immunoactivation. The profound depression of IgG2 in mothers suggests that IgG2 neonatal levels mostly reflect the maternal deficit rather than a selective impairment of IgG2 transfer.

Frailty as a predictor of mortality and hospital services use in older adults: a cluster analysis in a cohort study.

Background: Lowering mortality and hospitalization of older adults is one of the main goals of public health to improve both health systems' sustainability and older adults' quality of life. The aim of this study is to identify the determinants associated with mortality and the use of hospital services in the population older than 64 years of age. Methods: A randomized sample from the population of the Lazio region (Italy) above the age of 64 was enrolled in 2014 by the administration of a questionnaire to assess frailty; the rates of use of hospital services and mortality in the year following the enrolment have been retrieved by the regional database. Univariable and multivariable analyses addressed the association of health status, social and economic variables with health outcomes. Results: One thousand two hundred and eighty persons were recruited; 52 deaths were reported at 1 year of follow-up (robust 1.8%, frail 10.1% and very frail 19.1%, P < 0.001). The mean rate of use of hospital services was 692.2 per 1000 observation/year (robust 589.5, frail 1191.1 and very frail 848.4, P < 0.001). In the multivariate analysis, the higher rate of use of hospital services was independently associated with functional status, social support, psychological/psychiatric discomfort, availability of home care services and physical health. Conclusions: Frailty, as a multidimensional issue, is also a strong predictor of survival in the short term. The use of the hospital services by older adults is associated mainly with functional status, social resources, psycho-physical status and health service organization factors.

Antibody response to hepatitis B vaccine in HIV-exposed infants in Malawi and correlation with HBV infection acquisition.

The aim of this study was to assess the immune response to HBV vaccine in HIV-exposed infants and to correlate it to HBV infection acquisition. Protective anti-HBs levels (>10 mIU/mL) were found in 54/58 (93.2%) infants at 6 months, 126/144 (87.5%) at 12 months and 141/176 (80.1%) children at 24 months. HBV infection (seven children were HBsAg + at Month 24) occurred also in the presence of levels above 10 mIU/mL. Our findings indicate limited impact of HIV exposure on anti-HBV immune response, but suggest that levels >10 mIU/mL may be required to confer protection in this context.

Soluble CD14 levels in plasma and breastmilk of Malawian HIV+ women: Lack of association with morbidity and mortality in their exposed infants.

PROBLEM: Data on soluble CD14 (sCD14) during pregnancy and lactation are scarce. We assessed the levels of sCD14 in plasma and breastmilk of Malawian HIV-positive women and evaluated the possible association with morbidity and mortality in the HIV-exposed children. METHOD OF STUDY: One hundred and forty-nine mother/child pairs were studied. Women received antiretroviral therapy from 26 weeks of gestation to at least 6 months of exclusive breastfeeding. sCD14 concentrations were determined using an enzyme-linked immunosorbent assay. RESULTS: sCD14 levels measured at 26 weeks of pregnancy (median: 1418 ng/mL, IQR: 1086-1757) were inversely correlated to maternal CD4+ cell count (r = -.283, P = .001) and to neonatal birthweight (r = -.233, P = .008). At 6 months, sCD14 plasma levels were significantly higher compared to baseline (1993 ng/mL, IQR: 1482-2604, P < .001), and breastmilk sCD14 levels (7668 ng/mL, IQR: 5495-10207) were 4-fold higher than in plasma (although the concentrations in the two compartments were not correlated). No association was found between sCD14 levels in plasma or breastmilk and morbidity or mortality in children. CONCLUSION: Higher sCD14 levels in HIV-positive women were associated with a more compromised maternal immunological status and to a lower neonatal birthweight, but not to poorer clinical outcomes in the HIV-exposed children.

[The progressive patient care program as a model of field training of public health practitioners: the experience of the Roman Public Health Academy]. / L'ospedale ad Intensità di cura come modello di formazione condivisa sul campo: l'esperienza dell'Accademia Romana di Sanità Pubblica.

The management of healthcare facilities has become increasingly complex in recent years, leading to a greater demand for public health physicians in Italy. Public Health physicians are responsible for evaluating community needs, with particular attention to health determinants and, at the same time, to final user feedback. During their training, they must acquire the competencies to manage a wide range of problems. The Roman Public Health Academy (ARSP) was developed to motivate young residents in Public Health to acquire the knowhow, skills and abilities required of a public health practitioner. It therefore implemented a special training program offering different educational opportunities for residents. In particular, the program offers a team of three young residents field training opportunities, allowing them to become engaged in solving complex technical and management problems. In this paper we describe the methods through which, following a specific request by the director of a hospital in Rome, the team supported a project involving the reorganization of several hospital wards. The aim of the reorganization was to enhance the performance and efficiency of the wards, according to the Progressive Patients Care program.

Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy in Mozambique.

BACKGROUND: Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. METHODS: At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. RESULTS: Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/µL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. CONCLUSIONS: The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation in very advanced HIV/tuberculosis disease.

Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: implications for the activity of next-line regimens from a longitudinal study in Mozambique.

BACKGROUND: We describe the accumulation of HIV-1 drug resistance and its effect on the activity of next-line components in patients with virological failure (HIV-1 RNA >1000 copies/mL) after 1 year (t1) of first-line antiretroviral therapy (ART) not switching to second-line drugs for one additional year (t2) in low-middle income countries (LMIC). METHODS AND RESULTS: We selected 48 patients from the DREAM cohort (Maputo, Mozambique); their median pre-ART CD4+ cell count was 165 cells/µl. At t1 patients were receiving ART since a median of 12.2 months (mainly zidovudine/lamivudine/nevirapine), their median HIV RNA was 3.8 log10 copies/mL, 43 (89.6%) presented at least one resistance-associated mutation (RAM), most frequently for lamivudine/emtricitabine, nevirapine and efavirenz. Resistance to tenofovir, was 10% at 1 year and higher than 20% at 2 years, while projection at 3 years was >30%. At t2, 42 (89.4%) had a predicted low-level or higher resistance to at least 1 s-line drug. At t1, the frequency of RAM in patients with a lower adherence to pharmacy appointments (<95%) was significantly lower (12/20, 60% for NRTI and 14/20, 70% for NNRTI) than in those with a better adherence (26/28, 92.8% for NRTI and 25/28, 89.3% for NNRTI) (OR 0.12, 95% CI 0.02-0.63, p = 0.012 and OR 0.28, 95% CI 0.06-1.29, p = 0.103, respectively). Overall thymidine analogue mutations (TAMs) accumulation rate was 0.32/year, 0.50/year in the subgroup with HIV RNA >10,000 copies/mL; NNRTI RAM accumulation rate was 0.15/year, 0.40/year in the subgroup with HIV RNA >10,000 copies/mL. CONCLUSIONS: While the activity of NNRTIs is compromised early during failure, tenofovir and zidovudine activity are reduced more frequently after 1 year of documented virological failure of thymidine analogue-based first-line ART, with RAMs accumulating faster in patients with higher viral loads. The present observation may help informing decisions on when to switch to a second line ART in patients on virological failure in LMIC.

High CMV IgG antibody levels are associated to a lower CD4+ RESPONSE to antiretroviral therapy in HIV-infected women.

BACKGROUND: Virtually all HIV-infected women in sub-Saharan Africa have evidence of Cytomegalovirus (CMV) infection and levels of specific anti-CMV IgG have been suggested to represent more intense reactivation of subclinical infection. Studies have also shown direct influence of CMV on lymphocytes. OBJECTIVE: The aim of this study was to determine if levels of anti-CMV specific antibodies could impact on the immunological response to antiretroviral treatment (ART) in HIV-infected pregnant women. STUDY DESIGN: CMV-specific IgG were measured in HIV-infected pregnant women at 26 weeks of gestation (before ART initiation). Women received ART until 6 months postpartum or indefinitely according to local guidelines at the time of the study. Immunological and virological responses were assessed 6 months and 24 months after delivery. RESULTS: A total of 81 women were studied. At baseline high levels (above the median) of specific IgG were associated to a low CD4+ cell count (P<0.001), a high viral load (P=0.003), and to an older age (P=0.051). In a multivariate model adjusting for baseline CD4+ count, baseline viral load and age, the presence of low levels of CMV IgG was the only independent predictor of a a CD4+ count above 500/mm3 24 months after delivery among women on continuous therapy. CONCLUSIONS: In this cohort, levels of CVM IgG had a significant influence on the immunological response to ART, adding information to the known impact of CMV infection in the HIV-positive population, and underlining the need of new strategies to contain the infection.

Impact of glutathione transferases genes polymorphisms in nevirapine adverse reactions: a possible role for GSTM1 in SJS/TEN susceptibility.

PURPOSE: Nevirapine (NVP) is used in developing countries as first-line treatment of HIV infection. Unfortunately, its use is associated with common serious adverse drug reactions, such as liver toxicity and the most severe and rare Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). GSTT1 and GSTM1 genes code for enzymes involved in the metabolism of a wide range of drugs. We hypothesized that this gene variability could be implicated in NVP adverse reactions. METHODS: We analyzed the GSTM1 and GSTT1 null genotypes by multiplex PCR in a population of 181 patients from Mozambique, treated with NVP. A case/control association study was performed. We also counted the number of risk alleles in SJS/TEN patients and in controls, including the GSTM1 null genotype and four previously identified risk alleles in CYP2B6, HCP5, and TRAF3IP2 genes. RESULTS: Among patients, 27 had developed SJS/TEN and 76 had developed hepatotoxicity during the treatment. The GSTM1 null genotype was more frequent in the cases with SJS/TEN than in the controls (OR = 2.94, P = 0.027). This association is also observed when other risk factors are taken into account, by a multivariate analysis (P = 0.024 and OR = 3.58). The risk allele counting analysis revealed a significantly higher risk for SJS/TEN in patients carrying three or four risk alleles. Moreover, all subjects with five or six risk alleles developed SJS/TEN, while subjects without any risk alleles were present only in the control group. CONCLUSIONS: We observed an association between GSTM1 and SJS/TEN susceptibility. Moreover, GSTM1 contributes to the definition of a genetic risk profile for SJS/TEN susceptibility.

Assessment of frailty in community-dwelling older adults residents in the Lazio region (Italy): A model to plan regional community-based services.

PURPOSE OF THE STUDY: The prevalence of frailty is expected to increase worldwide in parallel with demographic ageing. Despite this, little is known about the prevalence in different populations particularly community-based samples. This cross-sectional study evaluates the prevalence of frailty in a community-dwelling older adult population and describes a methodology to plan community-based interventions. METHODOLOGY: A random sample of 1331 older adults, resident in the Lazio-Region of Italy, were screened by trained public health nurses (PHNs) by administering a validated questionnaire (the Functional Geriatric Evaluation questionnaire). Prevalence of frailty was calculated using the Final Synthetic Score derived from the questionnaire's Final Score. Variables associated with frailty were selected through univariate and multivariate statistical analysis. RESULTS: Prevalence of frail (FS≥10,≤50) and very frail (FS<10) individuals was 13.9% and 7.6% respectively. Variables associated with frailty were age (older than 85 years), disability, living alone or the presence of a paid carer, lower education and neurological disorders like stroke, dementia, Parkinson disease and other neuropsychiatric diseases; Anaemia or cancer were also associated with a higher prevalence of frailty. DISCUSSION: The study provide a comprehensive picture of the prevalence of frailty and factors associated to this condition in community-dwelling older adults. On the basis of the study results, a plan of community-based services could address the needs of care of the elderly population. A trained team of PHNs may be the most appropriate personnel to carry out multidimensional frailty assessment in this setting.