Overdose mortality is the major adverse health effect of drug injection. The potential determinants of overdose death are poorly understood; the aim of this study was to investigate risk factors for overdose mortality among intravenous drug users (IVDU). A cohort of 4200 IVDU attending methadone treatment centres in Rome during the period 1980-1988, was enrolled. Data were collected from clinical records. Vital status and cause of death were ascertained as of 31 December 1988. A matched case-control analysis within the cohort was performed to identify risk factors of death from overdose. All overdose deaths were included as cases and four controls, matched on year of birth and sex, were selected for each case from among the cohort members still alive at the time of death of the corresponding case. In all, 81 deaths from overdose were identified as cases and compared with 324 controls. A high risk of overdose death occurred among subjects who left treatment compared with those still in treatment (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.82-6.90). The OR was particularly elevated in the first 12 months after drop-out compared with those retained in treatment (OR = 7.98, 95% CI: 3.40-18.73). The risk of overdose death was higher for unmarried compared with married people (OR = 2.48, 95% CI: 1.31-4.68); a higher risk of overdose death was also associated with lower educational status and younger age at first drug use, but such association was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Background Few data about predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS) are available. Methods Retrospective study including all patients admitted with COVID-19 in an Italian reference hospital for infectious diseases between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between duration of VS and probability of clinical outcomes was evaluated through inverse probability weighted Cox model. Results 536 subjects were included. Median duration of VS from symptoms onset was 18 days (IQR 12-26). The estimated 30-day probability of VC was 70.2% (95%CI:65-75). At multivariable analysis, patients with comorbidities (aIRR = 0.88, p = 0.004), lymphopenia at hospital admission (aIRR = 0.75, p = 0.032) and with moderate/severe respiratory disease (aIRR = 0.42, p < 0.001) had a lower chance of achieving VC. The development of moderate/severe respiratory failure (aOR = 2.65, p = 0.003), a delayed hospital admission after symptoms onset (aOR = 1.18, p < 0.001), having baseline comorbidities (aOR = 1.25, p = 0.019) and D-dimer >1000 ng/mL at admission (aOR = 1.76, p = 0.035) independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery (aHR = 2.17, p < 0.001) and reduced the probability of death/mechanical ventilation (aHR = 0.36, p = 0.002). Conclusions In this study, severity of respiratory disease, comorbidities, delayed hospital admission and inflammatory markers negatively predicted the achievement of VC, which resulted to be associated to better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially in presence of signs of severity or comorbidities.
BackgroundDrug metabolism via the cytochrome P450 (CYP450) system has emerged as an important determinant in the occurrence of several drug interactions (adverse drug reactions, reduced pharmacological effect, drug toxicities). In particular, CYP3A4 and CYP3A5 (interacting with more than 60% of licensed drugs) exhibit the most individual variations of gene expression, mostly caused by single nucleotide polymorphisms (SNPs) within the regulatory region of the CYP3A4 and CYP3A5 genes which might affect the level of enzyme production.In this study, we sought to improve the performance of sensitive screening for CYP3A polymorphism detection in twenty HIV-1 infected patients undergoing lopinavir/ritonavir (LPV/r) monotherapy.MethodsThe study was performed by an effective, easy and inexpensive home-made Polymerase Chain Reaction Direct Sequencing approach for analyzing CYP3A4 and CYP3A5 genes which can detect both reported and unreported genetic variants potentially associated with altered or decreased functions of CYP3A4 and CYP3A5 proteins. Proportions and tests of association were used.ResultsAmong the genetic variants considered, CYP3A4*1B (expression of altered function) was only found in 3 patients (15%) and CYP3A5*3 (expression of splicing defect) in 3 other patients (15%). CYP3A5*3 did not appear to be associated with decreased efficacy of LPV/r in any patient, since none of the patients carrying this variant showed virological rebound during LPV/r treatment or low levels of TDM. In contrast, low-level virological rebound was observed in one patient and a low TDM level was found in another; both were carrying CYP3A4*1B.ConclusionsOur method exhibited an overall efficiency of 100% (DNA amplification and sequencing in our group of patients). This may contribute to producing innovative results for better understanding the inter-genotypic variability in gene coding for CYP3A, and investigating SNPs as biological markers of individual response to drugs requiring metabolism via the cytochrome P450 system.
IntroductionReduced bone mass density (BMD) is a frequent observation in HIV-infected persons. Relationship between body mass index (BMI), weight, height and BMD was reported for many populations. In particular, BMI has been found to be inversely related to the risk of osteoporosis.MethodsThis is a cross-sectional, monocentric study where all HIV-infected patients referred to first DXA scan in clinical routine during 2010–2013 were included. Osteopenia and osteoporosis were defined by T- score <−1 and <−2.5, respectively. Patients were categorized according to WHO BMI classification: underweight <18.5 kg/m2; normal weight 18.5–24.9 kg/m2; over weight 25–29.9 kg/m2; obese >30 kg/m2. Statistical analysis was carried using logistic regression.ResultsA total of 918 patients were included: median age 49 years (IQR, 44–55); 59.4% male; 93% Caucasian. Median anthrometric characteristics were: 68 kg (IQR, 59–78); 1.7 m (IQR, 1.6–1.75); 23.5 kg/m2 (IQR, 21.4–26.2). Underweight was found in 5%, normal weight in 61%, overweight in 26% and obesity in 8% of patients. According to T-scores, 110 (11.2%) patients were osteoporotic and 502 (54.7%) had osteopenia. In the femoral neck area, the prevalence of osteoporosis was slightly lower (5.7%) than lumbar spine site (9.2%). Agreements between sites of T-scores for the diagnosis of osteoporosis were 26 and 172 and 346 for osteopenia and normal BMD values, respectively. T-scores at femoral neck or lumbar spine positively correlated with BMI (p<0.001) (Figure 1). Among predictors of osteopenia/osteoporosis, univariable analysis showed: older age (p<0.0001); lower weight (p<0.0001); increasing height (p<0.002). Patients underweight had a higher risk of osteopenia (p=0.02) as well as of osteoporosis (p=0.003). Patients with BMI above normal had a reduced risk of low BMD (osteopenia p<0.0001; osteoporosis p<0.03). Controlling for calendar year, gender, ethnicity, and age, BMI was confirmed as risk factor if below normal (AdjOR of osteopenia 2.42 [95% CI 1.16–5.07] p=0.02; AdjOR of osteoporosis 3.22 [95% CI 1.60–6.49] p=0.001). ConclusionsOur findings indicate that almost 66% of HIV-infected patients have subnormal bone mass. Further, as in other patient populations, in the HIV infection also low BMI is an important risk factor for osteopenia/osteoporosis. This finding highlights the compelling need for standardized screening actions, particularly in patients weighting below normal.
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