Dyslipidaemia in HIV-infected patients: association with adherence to potent antiretroviral therapy

Metabolic complications are being increasingly recognized among HIV-infected patients treated with potent combination antiretroviral therapies. We sought to assess the association of dyslipidaemia with adherence to protease inhibitor (PI) therapy and with the markers of clinical response to antiretroviral therapy (CD4 count, HIV RNA viral level) through a prospective, cross-sectional cohort study. Fifty-six HIV-infected patients who were already on, or who were started on PI-containing antiretroviral therapy were monitored for the development of dyslipidaemias. Therapy with PI-containing antiretroviral therapy was significantly associated with elevated serum triglyceride level (>250 mg/dl) (52% vs 8%, P=0.001). Patients with an adherence rate of at least 80% to a PI-containing regimen were significantly more likely to have elevated low density lipoprotein (LDL) cholesterol level as compared to patients with an adherence rate of <80% (79% vs 26%, P=0.03). Patients with an adherence rate of at least 80% to a PI-containing regimen were also significantly more likely to have severe hypertriglyceridaemia (>800 mg/dl) as compared to patients with an adherence rate of <80% (21% vs 4%, P=0.04). Viral load at the last study visit did not correlate with total cholesterol (r=-0.39, P=0.30), LDL cholesterol (r=0.57, P=0.30), or triglyceride level (r=0.55, P=0.20). However, there was a significant correlation between the last viral load and high density lipoprotein (HDL) cholesterol (r=0.79, P=0.035), i.e. lower viral load was associated with higher HDL cholesterol level. In conclusion, dyslipidaemia in patients with HIV infection was significantly associated with adherence to PI-containing antiretroviral therapy. Patients who are adherent to PI-containing regimens at least 80% of the time warrant close monitoring for the development of dyslipidaemia.     

Pneumonia in long-term care: a prospective case-control study of risk factors and impact on survival

BACKGROUND: Pneumonia is a major cause of morbidity and mortality in long-term care facilities. Prior studies of pneumonia have failed to identify risk factors potentially amenable to intervention. Our objectives were to (1) identify modifiable risk factors for the occurrence of pneumonia and (2) determine the long-term impact of pneumonia on survival. METHODS: We performed a case-control study among residents of a Veterans Affairs long-term care facility. Case patients included all patients developing pneumonia from 2 days to 1 year after admission. Control subjects were matched for admission date, level of nursing care, and dependence in activities of daily living. Patients were followed up for 2 years or until death or discharge from the facility. RESULTS: We identified 104 case-control pairs. Risk factors significantly associated with pneumonia included witnessed aspiration (odds ratio, 13.9; 95% confidence interval, 1.7-111.0; P =.01), sedative medication (odds ratio, 2.6; 95% confidence interval, 1.2-5.4; P =.01), and comorbidity score (odds ratio, 1.2; 95% confidence interval, 1.0-1.4; P =.05). Mortality due to pneumonia was 23% at 14 days. Patients with pneumonia had a significantly higher mortality than did controls at 1 year (75% vs 40%; P<.001); survival curves converged at 2 years. In a Cox proportional hazards regression model, an episode of pneumonia was independently associated with mortality during follow-up (odds ratio, 2.6; 95% confidence interval, 1.7-3.9; P<.001). CONCLUSIONS: Among long-term care patients closely matched for age, level of dependency, and duration of institutionalization, an episode of pneumonia is associated with significant excess mortality that persists for up to 2 years. Two identified risk factors, large-volume aspiration and receipt of sedating medication, are potentially amenable to intervention.     

Predictors and Outcomes of Renal Replacement Therapy After Left Ventricular Assist Device Implantation

ObjectiveTo examine the frequency and outcomes of patients requiring renal replacement therapy (RRT) early after left ventricular assist device (LVAD) implantation.Patients and MethodsWe examined use of in-hospital RRT and outcomes in consecutive adults who underwent continuous-flow LVAD implantation from February 15, 2007, through August 8, 2017. Logistic regression was used to examine predictors of RRT. The associations of RRT with outcomes were examined using Cox proportional hazards regression.ResultsOf 354 patients who underwent LVAD implantation, 54 (15%) required in-hospital RRT. Patients receiving RRT had higher preoperative Charlson Comorbidity Index values (median, 5 vs 4; P=.03), Model for End-Stage Liver Disease scores (mean, 19.0 vs 14.5; P<.001), right atrial pressure (mean, 19.1 vs 13.4 mm Hg; P<.001), and estimated 24-hour urine protein levels (median, 357 vs 174 mg; P<.001) and lower preoperative estimated glomerular filtration rate (eGFR) (median, 43 vs 57 mL/min; P<.001) and measured GFR using ¹²⁵I-iothalamate clearance (median, 33 vs 51 mL/min; P=.001) than those who did not require RRT. Approximately 40% of patients with eGFR less than 45 mL/min/1.73 m² and 24-hour urine protein level greater than 400 mg required RRT vs 6% with eGFR greater than45 mL/min/1.73 m² and without significant proteinuria. Lower preoperative eGFR, higher estimated 24-hour urine protein level, higher right atrial pressure, and longer cardiopulmonary bypass time were independent predictors of RRT after LVAD implantation. Of patients requiring in-hospital RRT, 18 (33%) had renal recovery, 18 (33%) required outpatient hemodialysis, and 18 (33%) died before hospital discharge. After median (Q1, Q3) follow-up of 24.3 (8.9, 49.6) months, RRT was associated with increased risk of death (adjusted hazard ratio [HR], 2.86; 95% CI, 1.90-4.33; P<.001) and gastrointestinal bleeding (adjusted HR, 4.47; 95% CI, 2.57-7.75; P<.001).ConclusionIn-hospital RRT is associated with poor prognosis after LVAD. A detailed preoperative assessment of renal function before LVAD may be helpful in risk stratification and patient selection.     

Modeling targeted layered containment of an influenza pandemic in the United States

Planning a response to an outbreak of a pandemic strain of influenza is a high public health priority. Three research groups using different individual-based, stochastic simulation models have examined the consequences of intervention strategies chosen in consultation with U.S. public health workers. The first goal is to simulate the effectiveness of a set of potentially feasible intervention strategies. Combinations called targeted layered containment (TLC) of influenza antiviral treatment and prophylaxis and nonpharmaceutical interventions of quarantine, isolation, school closure, community social distancing, and workplace social distancing are considered. The second goal is to examine the robustness of the results to model assumptions. The comparisons focus on a pandemic outbreak in a population similar to that of Chicago, with approximately 8.6 million people. The simulations suggest that at the expected transmissibility of a pandemic strain, timely implementation of a combination of targeted household antiviral prophylaxis, and social distancing measures could substantially lower the illness attack rate before a highly efficacious vaccine could become available. Timely initiation of measures and school closure play important roles. Because of the current lack of data on which to base such models, further field research is recommended to learn more about the sources of transmission and the effectiveness of social distancing measures in reducing influenza transmission.     

Genetic variation in the CYP2C monooxygenase enzyme subfamily shows no association with longevity in a German population

Cytochrome P450 enzymes, especially the CYP2C subfamily, are involved in the generation of reactive oxygen species and are regarded as susceptibility factors for age-related diseases. Furthermore, the CYP2C-encoding genes are known to be highly polymorphic, with a number of variants leading to changes in enzyme activity. These observations prompted us to investigate whether allelic variation in the CYP2C-encoding genes was associated with human longevity. In a comprehensive haplotype tagging approach, we genotyped 56 single nucleotide polymorphisms located in the CYP2C gene family (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) in our extensive collection of 1,384 long-lived individuals (centenarians and nonagenarians) and 945 younger controls. None of the tested single nucleotide polymorphisms showed a significant association with the longevity phenotype at the allele, genotype, or haplotype level. These results suggest that there is no notable influence of sequence variation in the CYP2C genes on longevity in the examined German population.     

Effects of nifedipine GITS and diuretics in isolated systolic hypertension--a subanalysis of the INSIGHT study

Aims: This study tested the effects on cardiovascular outcomes of treatments based on nifedipine gastrointestinal therapeutic system (GITS) compared with the diuretic combination co-amilozide in a pre-specified subset of patients with isolated systolic hypertension (ISH) enrolled in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study. Major findings: Of 6321 randomized patients, 1498 (23.7%) had ISH with a baseline mean BP of 173/88 mmHg in both treatment groups. Mean BP fell by 29/10 mmHg in the nifedipine and 30/10 mmHg in the diuretic group to a mean BP of 144/78 mmHg and 143/79 mmHg, respectively, at endpoint. The percentage of primary outcomes in patients with ISH was not significantly different between the two treatment groups (nifedipine GITS 6.0%, co-amilozide 6.6%). The number of ISH patients with composite secondary outcomes was 90 (12.2%) in the nifedipine GITS group and 110 (14.5%) in the co-amilozide group (not significant). The incidence rates of primary and secondary outcomes were similar in patients without ISH. Conclusion: In patients with ISH, nifedipine GITS and co-amilozide had similar effects on clinical outcomes and BP lowering. They lend support to international guidelines for the treatment of hypertension recommending the use of long-acting dihydropyridine calcium-channel blockers as one treatment option for patients with ISH.     

Clinical significance of renal function in hypertensive patients at high risk: results from the INSIGHT trial

BACKGROUND: Increasing evidence suggests renal involvement in hypertension-related cardiovascular and cerebrovascular complications. To assess this role of renal function in more detail, we studied the evolution of renal function and the relationship of renal function with mortality and morbidity in the Intervention as a Goal in Hypertension Treatment (INSIGHT) study. METHODS: The INSIGHT study was a double-blind, randomized, multicenter trial in patients with hypertension and at least 1 additional cardiovascular risk factor. Treatment consisted of nifedipine gastrointestinal therapeutic system, 30 mg/d, or hydrochlorothiazide-amiloride (25 mg/d of hydrochlorothiazide and 2.5 mg/d of amiloride hydrochloride). Primary outcome was a composite of cardiovascular death, myocardial infarction, heart failure, and stroke. Renal function was assessed by measuring creatinine clearance, serum creatinine level, and serum uric acid level and by the presence of proteinuria. RESULTS: Creatinine clearance fell more in nifedipine recipients than in hydrochlorothiazide-amiloride recipients. Renal insufficiency developed in 2% of nifedipine recipients and 5% of hydrochlorothiazide-amiloride recipients. Primary outcomes occurred in 15% of patients with increased serum creatinine levels and 6% of patients with normal levels (odds ratio [OR] 2.89; 95% confidence interval [CI], 1.92-4.36; P<.001). Primary outcomes were more likely in patients with low creatinine clearance (<60 mL/min) than in those with higher clearances (9% vs 5%, respectively [OR, 1.51, 95%CI, 1.22-1.88; P<.001]). CONCLUSIONS: Renal function is an important predictor of risk in hypertensive patients at high risk. Antihypertensive treatment with a long-acting dihydropyridine calcium channel blocker may better preserve renal function than would treatment with diuretics.     

Presence of methicillin resistant Staphylococcus aureus in respiratory cultures from cystic fibrosis patients is associated with lower lung function

The prevalence of methicillin resistant Staphylococcus aureus (MRSA) infections is increasing in both the general population and cystic fibrosis (CF) patients. We hypothesized that MRSA infection of the conductive airways as seen in CF would be associated with more severe disease than that seen with methicillin sensitive S. aureus (MSSA). To test this hypothesis, we used data from the Epidemiologic Study of Cystic Fibrosis (ESCF), a large observational study of CF patients in North America, to compare CF patients with MRSA in their respiratory tract cultures to those with MSSA. During a 1-year time period from January 1, 2001 to December 31, 2001, data from 20,451 patients were collected by the ESCF, and 1,834 (7.5%) patients had respiratory tract cultures that were positive for S. aureus only. Compared to patients with MSSA only, patients with MRSA only had significantly more airflow obstruction, as measured by forced expiratory volume in 1 sec (FEV1). The mean FEV1 for patients 6-17 years old with MRSA was 80.7% predicted compared to 89.4% in the MSSA group (P<0.001). The likelihood of hospitalization and treatment with oral, inhaled, and intravenous antibiotics were all significantly increased in patients with MRSA compared to those with MSSA. Similar results were seen in patients >or=18 years old. The results of our study highlight the growing clinical impact of MRSA infections in CF patients.     

Findings from an outbreak of carbapenem-resistant <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> emphasize the role of antibiotic treatment for cross transmission

Purpose

In January 2015, we noticed by rectal swab analyses that seven of 23 patients at an early rehabilitation ward had been colonized with carbapenem-resistant Klebsiella pneumoniae (CKP). Here, we describe risk factors for CKP acquisition.

Methods

In the present study, the outbreak is described and risk factors for CKP acquisition are examined, e.g., antibiotic treatment. Microbiological analyses including corresponding results were examined to study when colonization with CKP occurred and whether patients had suffered from diarrhea. To examine whether spread of bacteria was clonal, multi-locus sequence typing as well as Xbal macrorestriction and pulsed-field gel electrophoresis was performed. The presence of carbapenmase was examined by PCR analysis. Through univariate analysis of risk factors in the small study sample, the role of antibiotic consumption, isolation procedures, patient’s age, gender, and Barthel index on colonization was elucidated.

Results

Clonal spread of the novel sequence type (ST)2255 was identified. Additionally, one patient was colonized with Escherichia coli and Serratia marcescens, both resistant to carbapenems, while a further patient carried another carbapenem-resistant E. coli strain. In all isolates, carbapenemase gene bla _OXA-48 was found to be located on a conjugative plasmid (60 kb), suggesting in vivo transmission from CKP to E. coli and S. marcescens. Univariate tests indicated that antibiotic treatment was the only risk factor showing a significant association with being colonized by CKP. In addition, the likelihood of diarrhea appeared to be higher in this group. Antibiotic treatment was associated with CKP colonization, whereas patients´ age, gender, Barthel index at admission, and residence with a CKP-colonized roommate were not. Diarrhea also seemed to support to distribution of CKP.

Conclusions

In this small outbreak, antibiotic treatment seemed to be the predominant risk factor for monoclonal transmission of bla _OXA-48 positive CKP.