Publications

BACKGROUND

The malaria-specific T-cell response is believed to be important for protective immunity. Antimalarial chemoprevention may affect this response by altering exposure to malaria antigens.

METHODS

We performed interferon γ (IFNγ) ELISpot assays to assess the cellular immune response to blood-stage and pre-erythrocytic antigens longitudinally from 1 to 3 years of age in 196 children enrolled in a randomized trial of antimalarial chemoprevention in Tororo, Uganda, an area of high transmission intensity.

RESULTS

IFNγ responses to blood-stage antigens, particularly MSP1, were frequently detected, strongly associated with recent malaria exposure, and lower in those adherent to chemoprevention compared to nonadherent children and those randomized to no chemoprevention. IFNγ responses to pre-erythrocytic antigens were infrequent and similar between children randomized to chemoprevention or no chemoprevention. Responses to blood-stage antigens were not associated with subsequent protection from malaria (aHR 0.96, P = .83), but responses to pre-erythrocytic antigens were associated with protection after adjusting for prior malaria exposure (aHR 0.52, P = .009).

CONCLUSIONS

In this high transmission setting, IFNγ responses to blood-stage antigens were common and associated with recent exposure to malaria but not protection from subsequent malaria. Responses to pre-erythrocytic antigens were uncommon, not associated with exposure but were associated with protection from subsequent malaria.

BACKGROUND

Diabetes mellitus is a potent risk factor for urinary incontinence. Previous studies of incontinence in patients with diabetes have focused on younger, healthier patients. Our objective was to characterize risk factors for urinary incontinence among frail older adults with diabetes mellitus in a real-world clinical setting.

METHODS

We performed a cross-sectional analysis on enrollees at On Lok (the original Program for All-Inclusive Care of the Elderly) between October 2004 and December 2010. Enrollees were community-dwelling, nursing home-eligible older adults with diabetes mellitus (N = 447). Our outcome was urinary incontinence measures (n = 2602) assessed every 6 months as "never incontinent", "seldom incontinent" (occurring less than once per week), or "often incontinent" (occurring more than once per week). Urinary incontinence was dichotomized ("never" versus "seldom" and "often" incontinent). We performed multivariate mixed effects logistic regression analysis with demographic (age, gender and ethnicity), geriatric (dependence on others for ambulation or transferring; cognitive impairment), diabetes-related factors (hemoglobin A1c level; use of insulin and other glucose-lowering medications; presence of renal, ophthalmologic, neurological and peripheral vascular complications), depressive symptoms and diuretic use.

RESULTS

The majority of participants were 75 years or older (72%), Asian (65%) and female (66%). Demographic factors independently associated with incontinence included older age (OR for age >85, 3.13, 95% CI: 2.15-4.56; Reference: Age <75) and African American or other race (OR 2.12, 95% CI: 1.14-3.93; Reference: Asian). Geriatric factors included: dependence on others for ambulation (OR 1.48, 95% CI: 1.19-1.84) and transferring (OR 2.02, 95% CI: 1.58-2.58) and being cognitively impaired (OR 1.41, 95% CI: 1.15-1.73). Diabetes-related factors associated included use of insulin (OR 2.62, 95% CI: 1.67-4.13) and oral glucose-lowering agents (OR 1.81, 95% CI: 1.33-2.45). Urinary incontinence was not associated with gender, hemoglobin A1c level or depressive symptoms.

CONCLUSIONS

Geriatric factors such as the inability to ambulate or transfer independently are important predictors of urinary incontinence among frail older adults with diabetes mellitus. Clinicians should address mobility and cognitive impairment as much as diabetes-related factors in their assessment of urinary incontinence in this population.

Alzheimer's disease (AD) is a prevalent and currently incurable brain disease whose impact will continue to rise as the population ages. With limited treatment options, a variety of experimental therapies are currently in clinical trials. EVP-6124 (encenicline) is an α7 nicotinic acetylcholine receptor partial agonist under investigation for the symptomatic treatment of AD. EVP-6124 activates the α7 nicotinic acetylcholine receptor at low nanomolar brain concentrations and improves memory performance in rats. Treatment with EVP-6124 in Phase I and II trials involving patients with mild-to-moderate AD was well tolerated and showed statistically significant improvements compared with placebo on cognitive and functional measures. Two Phase III trials under the title COGNITIV AD will assess the efficacy and tolerability of EVP-6124 in patients with mild-to-moderate AD. Based on the completed clinical trials and proposed mechanism of action, EVP-6124 would appear to be a good candidate for therapy in combination with cholinesterase inhibitors.

PURPOSE

Previous studies analyzing the relationship between Body Mass Index (BMI) and complications after partial nephrectomy have been underpowered. We use a national surgical database to explore the association of BMI with postoperative outcomes for Open Partial Nephrectomy (OPN) and Minimally Invasive Partial Nephrectomy (MIPN).

PATIENTS AND METHODS

Years 2005-2012 of the National Surgical Quality Improvement Program (NSQIP) were queried for OPN and MIPN. Postoperative complications were organized according to Clavien Grades and compared across normal weight (BMI kg/m(2)=18.5-<25.0), overweight (BMI=25.0-<30.0), and obese (BMI≥30.0) patients using standard descriptive statistics and multivariate regression modeling.

RESULTS

Of 1667 OPNs and 2018 MIPNs, 46.2% of patients were obese. Operative time was 16.91 minutes longer on average for obese patients (p<0.001). The overall complication rate after OPN was 17.9%, 17.2%, and 17.9% (p=0.945) for normal weight, overweight, and obese patients, respectively; while the overall complication rate after MIPN was 6.9%, 6.3%, and 8.7% (p=0.147). Multivariate regression analysis demonstrated that overweight and obese patients were not at increased risk for any complication grade after OPN and MIPN compared to normal weight patients. When comparing procedures, MIPN had a lower complication rate compared to OPN for obese (8.7% vs 17.9%, p<0.001) and morbidly obese patients (9.2% vs 22.2%, p=0.001).

CONCLUSIONS

Although surgery in obese patients is longer compared to normal weight patients, it does not appear to increase the likelihood of 30-day postoperative complications for OPN or MIPN. However, obese patients undergoing MIPN had lower complication rates than those undergoing OPN.

BACKGROUND

Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult volunteers were assessed for pneumococcal carriage by culture of nasal wash samples (NWS). Those without natural pneumococcal carriage received an intranasal pneumococcal inoculation with serotype 6B or 23F. The composition of the nasopharyngeal microbiome was longitudinally studied by 16S rDNA pyrosequencing on NWS collected before and after challenge.

RESULTS

Among 40 selected volunteers, 10 were natural carriers and 30 were experimentally challenged. At baseline, five distinct nasopharyngeal microbiome profiles were identified. The phylogenetic distance between microbiomes of natural pneumococcal carriers was particularly large compared to non-carriers. A more diverse microbiome prior to inoculation was associated with the establishment of pneumococcal carriage. Perturbation of microbiome diversity upon pneumococcal challenge was strain specific. Shifts in microbiome profile occurred after pneumococcal exposure, and those volunteers who acquired carriage more often diverted from their original profile. S. pneumoniae was little prominent in the microbiome of pneumococcal carriers.

CONCLUSION

Pneumococcal acquisition in healthy adults is more likely to occur in a diverse microbiome and appears to promote microbial heterogeneity.