Impact of diabetes and periodontal status on life quality.

OBJECTIVES: To investigate impact of periodontal status on quality of life (QoL) in type-1 (T1D) and type-2 (T2D) diabetes patients pre- and post-periodontal treatment using the Well-being Questionnaire 12 (W-BQ12) and Audit of Diabetes-Dependent Quality of Life-19 (ADDQoL-19). METHODS: W-BQ12 and ADDQoL-19 were self-completed by 56 T1D and 77 T2D patients at baseline and by those with periodontitis 3 and 6-months after therapy. RESULTS: At baseline, T1D patients had significantly higher general W-BQ12 [Median (IQR); 24.00 (20.25-27.75)] and positive well-being scores [8.00 (6.00-9.00)] (indicating better QoL) compared to T2D patients [22.00 (15.50-26.00) and 6.00 (3.50-9.00)], respectively (p < 0.05). Within both groups, general W-BQ12 scores did not differ significantly between patients with periodontal health, gingivitis, or periodontitis (p > 0.05). Significantly higher general W-BQ12 scores were observed in T1D patients at month 3 [28.00 (22.00-29.50)] compared to baseline [22.00 (17.00-24.50)] (p < 0.01), suggesting an initial improvement in QoL post-treatment. ADDQoL-19 identified that diabetes had greatest impact on the domain 'freedom to eat', with participants placing most importance on 'family life'. No significant changes in ADDQoL-19 scores were seen post-treatment (p > 0.05). CONCLUSIONS: Diabetes had impacts upon aspects of life quality in both T1D and T2D patients, though any additional impact based on periodontal status was not observed when using W-BQ12 and ADDQoL-19.

Comparing the influence of 2009 versus 2016 ASE/EACVI diastolic function guidelines on the prevalence and echocardiographic characteristics of preclinical diastolic dysfunction (stage B heart failure) in a Hispanic population with type 2 diabetes mellitus.

AIMS: To identify prevalence and predictors of undetected pre-clinical diastolic dysfunction (PDD) in a cohort of adult Hispanic patients with type 2 diabetes (T2D), and compare variations in epidemiology and echocardiographic characteristics between categorization based on the 2009 versus 2016 guidelines. METHODS: From 2013 to 2016, a cross-sectional cohort study of adults with T2D was performed. Patients without signs/symptoms of heart failure (HF) underwent 2D/Doppler echocardiographic screening, and were grouped into two subcohorts: 1) normal diastolic function, and 2) PDD, defined by the 2009 or 2016 ASE/EACVI criteria. RESULTS: Among 307 Hispanic subjects, by 2009 criteria, 193 (62.9%) had normal diastolic function, 113 (36.8%) diastolic dysfunction and 1 (0.3%) indeterminate. Those that had diastolic dysfunction (DD) were older (mean age 59.1 ±â€¯12.7 vs 52.2 ±â€¯12.2 years, p< 0.0001), with higher proportion female (69.0 vs 53.9%, p = 0.0092), and higher systolic blood pressure (136.5 ±â€¯18.6 vs 131.7 ±â€¯19.9, p = 0.0372). By 2016 criteria, 261 (85%) had normal diastolic function, 22 (7.2%) diastolic dysfunction and 24 (7.8%) indeterminate. Among those that had normal diastolic function (n = 261) by 2016 criteria, 29% (n = 76) had DD by 2009 criteria, and they were more likely to have higher E/e' and left atrial volume index (LAVI). CONCLUSIONS: By applying the 2016 versus the 2009 diastolic function criteria to a Hispanic population with T2D, the prevalence of PDD decreased significantly from 37% to 7%. These findings are consistent with recent studies demonstrating that the 2016 ASE/EACVI guidelines are more specific for diagnosing DD and hence less sensitive leading to lower prevalence of diastolic dysfunction.

Standardized screening for periodontitis as an integral part of multidisciplinary management of adults with type 2 diabetes: an observational cross-sectional study of cohorts in the USA and UK.

OBJECTIVE: To determine prevalence and factors predictive of periodontitis by using a standardized assessment model in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed an observational cross-sectional study to determine the burden of periodontitis in adults with type 2 diabetes attending urban, ambulatory referral centers in the USA and UK. Full-mouth probing was performed and periodontitis was diagnosed based on either a low (≥5 mm at ≥1 site) or high pocket probing-depth threshold (≥6 mm at ≥1 site). Results were stratified into a five-stage schema and integrated with other clinical variables into the novel Diabetes Cross-Disciplinary Index to function as a balanced health scorecard. Corresponding demographic and routinely collected health data were obtained and comparisons were made between patients with and without periodontitis. Multivariable logistic regression was performed to identify factors predictive of the presence or absence of periodontitis. RESULTS: Between our two cohorts, 253 patients were screened. Caucasians comprised >90% and Hispanic Americans >75% of the UK and US cohorts, respectively. Males and females were equally distributed; mean age was 53.6±11 years; and 17 (6.7%) were edentulous. Of the 236 dentate patients, 128 (54.2%) had periodontitis by low threshold and 57 (24.2%) by high threshold. Just 17 (7.2%) were periodontally healthy. No significant differences in age, HbA1c, blood pressure, body mass index, low-density lipoprotein cholesterol, or smoking status (all p>0.05) were identified between those with or without periodontitis (regardless of threshold) and none was found to be a significant predictor of disease. CONCLUSIONS: Periodontitis is frequent in adults with type 2 diabetes and all should be screened. Periodontal health status can be visualized with other comorbidities and complications using a novel balanced scorecard that could facilitate patient-clinician communication, shared decision-making, and prioritization of individual healthcare needs.

PEGylated liposomal vancomycin: a glimmer of hope for improving treatment outcomes in MRSA pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) plays a significant role in the pandemic of multidrug resistant bacterial infections and is a major cause of hospital-acquired pneumonia. MRSA pneumonia carries a high morbidity and mortality rate especially in elderly diabetics with chronic kidney disease. S. aureus is highly virulent and successful respiratory pathogen. Vancomycin and linezolid are the only two antimicrobial agents FDA-approved to treat MRSA pneumonia. Standard vancomycin dosing is associated with high clinical failure rates and higher dosages are associated with increased nephrotoxicity. Pharmacokinetic and pharmacodynamic limitations are major contributors to poor outcomes with vancomycin. New agents are needed to improve treatment outcomes with MRSA pneumonia. Recently released antimicrobials with in vitro activity are not FDA-approved for treating MRSA pneumonia. Other novel agents are being investigated though none are in late-stage development. Pharmaceutical industry perception of low returns on investment, a Sisyphean regulatory environment, and obstacles to patentability have contributed to declining interest in both the development of novel antibiotics and the improvement of existing generic formulations. Despite decades of investigation into liposomal encapsulation as a drug delivery system that would increase efficacy and decrease toxicity, only liposomal amphotericin B and doxorubicin are commercially available. In this article, the pharmacokinetics and biodistribution of a novel PEGylated liposomal vancomycin formulation along with passive targeting and the enhanced permeability and retention effect of liposomal drug delivery; the pathogenesis of MRSA pneumonia; and recent patents of novel anti-MRSA agents, including inhalational liposomal vancomycin, are reviewed.

Development and stability studies of novel liposomal vancomycin formulations.

A promising strategy to improve the therapeutic efficiency of antimicrobial agents is targeted therapy. Although vancomycin has been considered a gold standard for the therapy of MRSA pneumonia, clinical failure rates have also been reported owing to its slow, time-dependent bactericidal activity, variable lung tissue penetration and poor intracellular penetration into macrophages. Liposomal encapsulation has been established as an alternative for antimicrobial delivery to infected tissue macrophages and offers enhanced pharmacodynamics, pharmacokinetics and decreased toxicity compared to standard preparations. The aim of the present work is to prepare vancomycin in two different liposomal formulations, conventional and PEGylated liposomes using different methods. The prepared formulations were optimized for their particle size, encapsulation efficiency and physical stability. The dehydration-rehydration was found to be the best preparation method. Both the conventional and PEGylated liposomal formulations were successfully formulated with a narrow particle size and size distribution and % encapsulation efficiency of 9 ± 2 and 12 ± 3, respectively. Both the formulations were stable at 4°C for 3 months. These formulations were successfully used to evaluate for their intracellular killing of MRSA and in vivo pharmacokinetic and bio-distribution studies.

PEGylated liposome encapsulation increases the lung tissue concentration of vancomycin.

Pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) often cannot be cured by vancomycin treatment. Poor lung tissue and intracellular penetration limits the ability to achieve effective bactericidal levels, particularly in alveolar macrophages, where MRSA can evade phagocytic killing. Compared to standard formulations, liposome encapsulation has been shown to enhance vancomycin intracellular killing of MRSA. In this murine pharmacokinetic and biodistribution study, PEGylated liposomal vancomycin, compared to standard and non-PEGylated formulations, significantly prolonged blood circulation time and increased deposition in lung, liver, and spleen and yet reduced accumulation in kidney tissue. As a result of optimizing antimicrobial targeting of infected lung tissue and limiting renal parenchymal exposure, administration of PEGylated liposomal vancomycin may improve the efficacy of treatment of MRSA pneumonia and reduce the risk of nephrotoxicity.