Efficacy evidences in prevention of HIV infection in developing countries. A critical appraisal from population-based studies

For generalised HIV/AIDS sub-Saharan African epidemics emphasis has been placed on the three established pillars of HIV prevention: condom promotion and distribution, Voluntary Counselling and Testing (VCT) and treatment of other sexually transmitted infections (STIs). Experiences in several countries support the positive results of Ugandan prevention politics called Abstinence, Be faithful, Condom (ABC), based on Primary Behaviour Change (PBC). Polemics tending to label this approach as “confessional based” have been recently intensified after Pope Benedict XVI recalled how the sole use of condoms cannot be considered the solution for HIV/AIDS in Africa. An honest and scientific approach to the dramatic reality of HIV/AIDS in Africa may yet require a reconsideration of the Western positions towards HIV prevention, accepting the potential challenge of a multifaceted strategy that uses all valid approaches, with particular regard to PBC: the elusive goal of vaccine, the simplistic trust in condoms, or acritical enthusiasm in drugs (either as therapy, postexposure or preventive treatment), mathematical modelling. All these are pieces of a complex puzzle. Synergy between treatment and prevention needs to be implemented in a realistic way, never forgetting that behaviour change is a process, not an event, involving human freedom and will. The need of a really participating community, with a prevention coming from below to the top and not from external over-imposing criteria, is also mandatory.     

Therapy of chronic hepatitis C: a critical review

Combination therapy (Interferon plus ribavirin) is the current therapeutic gold standard for naive Hepatitis C Virus (HCV)-positive patients and with the recent advent of pegylated (PEG) IFN the rate of the sustained virological response (HCV-RNA clearance 6 months after the end of treatment) is about 54%-56% with a therapeutical gain mainly among patients with unfavourable HCV genotype (1a, 1b); in this subset of patients, a 42%-46% sustained response rate is achieved compared with 33%-36% found among genotype 1 patients treated with the standard therapy. Patients who respond to IFN monotherapy but relapse during the follow-up should be re-treated with combination therapy given for at least 6 months at the minimum dose of 3 MU thrice weekly plus ribavirin 1000 mg/daily. Recent data suggest that prolonging the time of treatment (12 months) may induce a significantly higher rate of sustained response among patients with genotype 1. The efficacy of the combination of IFN and ribavirin in retreating patients with chronic hepatitis C not responding to IFN monotherapy is controversial as it ranges between 0% and 40%. Recent data show an overall rate of sustained response of 23% when an aggressive approach is adopted but increasing the dosage and the time of treatment induces a significant therapeutic benefit only in patients with genotype 1. In conclusion, a therapeutic progress for chronic hepatitis C has been achieved during the last 10 years (56% vs 20% of sustained response rate obtained with IFN monotherapy) but several unresolved issues are yet to be addressed.     

Effect of nomifensine on motor activity,dopamine turnover rate and cyclic 3′, 5′-adenosine monophosphate concentrations of rat striatum

Summary Nomifensine (8-amino-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline hydrogenmaleate) is a new antidepressant with a pharmacological profile somewhat different from the classical tricyclic antidepressants.In doses higher than 1 mg/kg it increases motor activity in rats, an effect wich resembles that of amphetamines. Unlike amphetamine, its effect on motor activity cannot be blocked by pretreatment with -methyltyrosine methylester (-MT), only the combined pretreatment with -MT and reserpine abolishes the stimulatory effect of nomifensine.Dopamine (DA) and Norepinephrine (NE) turnover are not increased by threshold doses of nomifensine which elicit hypermotility, only a tenfold higher dose is able to increase DA and NE turnover in striatum and teldiencephalon significantly. In contrast, (+)amphetamine increases DA turnover in striatum in threshold doses, which also increase motor activity and apomorphine decreases DA turnover in striatum in behaviorally active doses.Nomifensine, (+)amphetamine and apomorphine increase 3, 5-adenosinemonophosphate (cAMP) concentrations in rat striatum in a dose dependent manner. However the cAMP increment elicited by (+)amphetamine is dose dependent only within a limited range and reaches maximal values after 2.5 mg/kg, whereas nomifensine and apomorphine exhibit a linear dose response relationship between 5 and 15 mg/kg.These results are consistent with evidence from studies on NE and DA uptake and release in synaptosomes, which indicate, that nomifensine blocks NE uptake in noradrenergic and DA uptake in dopaminergic neurons very strongly. Inhibition of DA uptake in striatum, which is very poor in tricyclic antidepressants, may be responsible for the stimulatory effect of nomifensine on motor activity. Since nomifensine fails to increase DA turnover in strtiatum in doses, which elicit hypermotility, a DA release from dopaminergic neurons—as described for amphetamine-is unlikely to cause this behavior activation.     

Lymph node dissection should not be dismissed in case of localized renal cell carcinoma in the presence of larger diseases

Objective

To assess whether even in the group of localized renal cell carcinoma (RCC), some patients might harbor a disease with a predilection for lymph node invasion (LNI) and/or lymph node (LN) progression and might deserve lymph node dissection (LND) at the time of surgery.

The key role of time in predicting progression-free survival in patients with renal cell carcinoma treated with partial or radical nephrectomy: Conditional survival analysis

IntroductionIn surgically treated patients with renal cell carcinoma (RCC), the progression-free survival (PFS) rate may significantly change according to the progression-free postoperative period. To test this hypothesis, we set to evaluate the conditional PFS rate in surgically treated patients with RCC.MethodsWe evaluated 1,454 patients with RCC, surgically treated between 1987 and 2010, at a single institution. Cumulative survival estimates were used to generate conditional PFS rates. Separate Cox regression models were fitted to predict clinical-progression risk in patients who were progression free from 1 to 10 years after surgery.ResultsDuring the immediate postoperative period, the 5-year PFS rate was 88%, and it increased to 92%, 94%, and 97% in patients who remained progression free at, respectively, 1, 5, and 10 years after surgery. At multivariable analyses, where patients with stage I disease were considered as a reference, the highest clinical-progression risk was observed at the eighth postoperative year in patients with stage II disease (hazard ratio [HR]: 2.9) and during the immediate postoperative period in patients with stage III to IV disease (HR: 5.5). In comparison with patients with grade I disease, the highest clinical-progression risk was observed at the fourth (as well as eighth) postoperative year in patients with grade II disease (HR: 5.7), sixth postoperative year in patients with grade III disease (HR: 7.2), and during the immediate postoperative period in patients with grade IV disease (HR: 8.5).ConclusionsThe postoperative progression-free period has an important effect on the subsequent clinical-progression risk. This aspect should be considered along with tumor characteristics to plan the most cost-effective follow-up scheme for surgically treated patients with RCC.     

Clinical and epidemiological features of HIV/AIDS infection among migrants at first access to healthcare services as compared to Italian patients in Italy: a retrospective multicentre study, 2000–2010

Purpose

Migrants account for approximately 8.7 % of the resident population in Italy. The immigration status deeply influences access to prevention and care, thus contributing to increase the burden of HIV/AIDS among such a fragile category. The aim of this study was to investigate socio-demographic and baseline clinical and immunological features of HIV-infected migrants, as compared to Italians.

Methods

We retrospectively analysed data for all the 1,611 HIV-infected migrant patients and a random sample of 4,230 HIV-infected Italian patients aged 18 or older who first accessed nine Italian clinical centres in 2000–2010 and were followed up at least 1 year. Differences in baseline characteristics between migrants and Italians were evaluated in univariate analysis, while factors associated with late presentation were evaluated in multivariate analysis using logistic regression models.

Results

The baseline profile differs between the HIV-infected migrant and Italian patients, substantially reflecting what reported by current statistics in terms of gender, age, risk category as well as clinical features. Late presenters were more frequent among migrants as compared to Italians (53.0 vs 45.8 %; adjusted odds ratio [(AOR) = 1.55, 95 % confidence interval (CI) 1.34–1.78]. Other factors associated with late presentation included increasing age, as well as undocumented legal status among foreign-born subjects (AOR = 1.41, 95 % CI 0.97–2.04), though of borderline significance.

Conclusions

Late presentation still represents a relevant problem despite the advances in the management of HIV infection. More efforts are needed to allow early diagnosis and access to care among the most vulnerable, such as undocumented foreign-born subjects in a country where migration flows are on the rise.     

Clinical utility of PPPM and FPS-R to quantify post-tonsillectomy pain in children

Objectives

As pain is a subjective and difficult parameter to assess in children, we aimed to evaluate the correspondence of two pain scales – parents’ post-operative pain measure (PPPM) and faces pain scale-revised (FPS-R) with analgesic intake in the assessment of post-tonsillectomy pain in a pediatric population.

Methods

Children aged 4–10 years (n = 174) undergoing tonsillectomy with or without adenoidectomy had their pain monitored by PPPM and FPS-R over 7 days following surgery. The amount of analgesic (acetaminophen or dipyrone) intake was also recorded each day. Linear regression and correlation analysis were performed for pain scales and Poisson regression model for analgesic administration. To evaluate influence of gender linear regression and logistic regression with random effects were performed.

Results

PPPM and FPS-R presented a significant positive correlation (τ = 0.5; R² = 0.36; p < 0.001). PPPM and FPS-R also showed a significant correlation with analgesic use over the 7 post-operative days (p < 0.0001). No influence of gender was observed in pain levels by both scales.

Conclusions

Our data demonstrate that PPPM and FPS-R are equivalent pain scales to quantify post-tonsillectomy pain in children and are useful tools in post-tonsillectomy clinical research.     

Safety and durability in a cohort of HIV-1 positive patients treated with once and twice daily darunavir-based therapy (SCOLTA Project)

Objective

To evaluate safety and durability of once-daily and twice-daily darunavir/ritonavir (DRV/r)-based treatment in HIV patients in clinical practice.

Methods

The Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) project is a prospective, observational, multicenter cohort created to assess the incidence of adverse events in patients receiving new antiretroviral drugs. Twenty-five Italian infectious diseases centers enroll patients and collect their data through this on-line system. Periodical evaluations of these patients, including physical examination and laboratory tests, were performed at baseline and every 6 months.

Results

Four hundred and twenty-nine patients were enrolled since May 2006. Eighty-five patients (19.8%) were prescribed once-daily DRV/r; 31 of them were treatment-naïve (36.5%). Among 54 (63.5%) treatment-experienced patients, 21 (38.9%) had undetectable viral load and started once-daily DRV/r as a simplification regimen. Patients on twice-daily regimen were older, more frequently lipodystrophic, HCV-coinfected, and in CDC stage C. In the following 24 months of follow-up, the viral load steadily decreased as well as the CD4 cell count rose. The reason for discontinuation did not significantly differ between groups. Mean blood glucose (BG) change from baseline did not show significant difference between groups, as well as high density lipoprotein cholesterol (HDL-C), triglycerides (TGL) and alanine transaminase (ALT). The survival curve shows that patients in the once-daily regimen withdrew treatment more frequently than those on twice-daily regimen (Log Rank Chi²P = 0.009).

Conclusion

Our study showed that DRV/r administrated both once daily or twice daily was safe and well tolerated with few discontinuations due to adverse events.     

Prophylaxis of hepatitis B virus recurrence after liver transplantation in carriers of lamivudine-resistant mutants.

The combination of lamivudine and hepatitis B immunoglobulin (HBIG) reduces the risk of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, the efficacy of this strategy and the need for combined therapy with adefovir dipivoxil (ADV) in patients who select lamivudine-resistant strains (YMDD) before surgery is still unknown. Twenty-two patients treated with lamivudine (LAM) who underwent LT after YMDD-mutant selection were studied. In 13 patients, YMDD mutants were associated with an HBV DNA breakthrough greater than 5 log10 (group A: phenotypic resistance), and 11 were treated with ADV to decrease viral load before LT. In the remaining 9 patients who did not experience the viral breakthrough, YMDD mutants were detected only retrospectively in sera stored at the time of LT (group B: genotypic resistance). During 35 months of post-LT follow-up, none of the 11 patients of group A treated with ADV before and after surgery (in addition to HBIG and LAM) had HBV recurrence, and neither did any of the 7 subjects of group B treated with LAM before and after transplantation (in addition to HBIG). HBV recurred in 2 patients of group A (untreated with ADV before surgery and transplanted with an HBV DNA exceeding 5 log10) and in 2 subjects of group B (who spontaneously stopped HBIG after surgery). In carriers of YMDD mutants, the risk of post-LT HBV recurrence is low, provided that preemptive and prophylactic ADV (in addition to LAM and HBIG) treatment is used in highly viremic patients and prophylactic LAM (or ADV) and HBIG therapy is continued in low viremic patients.