Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development.

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P < 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes.

Inpatient, Outpatient, and Pharmacy Costs in Patients With and Without HIV in the US Veteran's Affairs Administration System.

OBJECTIVES: To evaluate the association between human immunodeficiency virus (HIV) patients and medical costs (inpatient, outpatient, pharmacy, total) using a national cohort of HIV-infected Veterans and non-HIV matched controls within the Veteran's Affairs (VA) Administration system. DESIGN: This study used claims (January 2000 to December 2016) extracted from the VA Informatics and Computing Infrastructure and VA Health Economics Resource Center. Cases included Veterans with an International Classification of Diseases, Ninth Revision/International Classification of Diseases, Tenth Revision for HIV with at least 1 prescription for a complete antiretroviral therapy regimen (January 2000 to September 2016). Two non-HIV controls were exact matched on race, sex, month, and year of birth. All patients were followed until the earliest of the following: last date of VA activity, death, or December 31, 2016. RESULTS: A total of 79 578 patients (26 526 HIV and 53 052 non-HIV) met all study criteria. The average age was 49.3 years, 38% were black, 32% were white, and 97% were male for both the HIV and control cohorts. Adjusted multivariable logistic regression models demonstrated that HIV was associated with higher odds of incurring a pharmacy cost (odds ratio = 2286.45, 95% confidence interval: 322.79-16 195.82), 4-fold, and 2-fold higher odds of incurring both outpatient and inpatient costs compared to the matched controls, respectively. In adjusted multivariable gamma generalized linear models, HIV-positive patients had an almost 4-fold, 17-fold, and almost 2-fold higher cost than matched controls in total, pharmacy, and outpatient costs, respectively. CONCLUSIONS: This study found an association between HIV-positive patients having higher odds of incurring a medical cost as well as higher medical costs compared to non-HIV controls.

Cost-Effectiveness Analysis of Early vs Late Diagnosis of HIV-Infected Patients in South Carolina.

OBJECTIVES: It is anticipated that early diagnosis, linkage to care, initiation of antiretroviral therapy (ART), and retention in care would lead to reduced opportunistic infections, reduction in human immunodeficiency virus-related morbidity and mortality and reduced rates of HIV transmission. This would be expected to lead to a reduction in the lifetime cost of care (LCC). This study analyzed existing data to determine to what extent early-versus-late HIV diagnosis affects LCC. METHODS: The South Carolina Department of Health and Environmental Control electronic HIV/acquired immunodeficiency syndrome reporting system data were used for this study. The first CD4 and viral load reported to the Enhanced HIV/AIDS Reporting System of the Centers for Disease Control and Prevention are considered the initial CD4 and viral load. Late HIV diagnosis was based on a CD4 count ≤200 at diagnosis. A previously validated simulation model developed by the John Snow Institute for the South Carolina Department of Health and Environmental Control was used to determine the discounted LCC. Comparisons were made between late and early HIV diagnosis. RESULTS: From 2013 through 2015, 2138 individuals were diagnosed as having HIV in South Carolina; 180 individuals were excluded from further analysis because an initial CD4 count was missing. Final analysis was based on 1958 individuals. Late HIV diagnosis occurred in 509 individuals (26%). When stratified based on CD4 count at diagnosis, the discounted LCC per person in those with an initial CD4 count ≤200 was $262,374 and in those with an initial CD4 count >500 was $416,766. Those with lower CD4 counts at diagnosis had more lost quality-adjusted life-years (QALYs; 7.95 QALYs lost per person with an initial CD4 count ≤200 compared with 4.45 QALYs lost per person with an initial CD4 count >500), more lifetime HIV transmissions (1.4 per person with an initial CD4 count ≤200 compared with 0.72 per person with an initial CD4 count >500), and lower additional life expectancy (30.73 additional years with an initial CD4 count ≤200 compared with 38.08 additional years with an initial CD4 count >500). CONCLUSIONS: Although individuals with lower CD4 counts at diagnosis had a lower discounted LCC, they had more lost QALYs, more lifetime HIV transmissions, and lower additional life expectancy.

Clostridium tertium Peritonitis and Concurrent Bacteremia in a Patient With a History of Alcoholic Cirrhosis.

Spontaneous bacterial peritonitis (SBP) is a recognized cause of morbidity and mortality in cirrhotic patients. Enterobacteriaceae have been isolated from the majority of peritonitis cases and the gram negative aerobe Escherichia coli is the most commonly isolated organism. Anaerobic organisms are rarely isolated because of the high oxygen tension in ascetic fluid. We report a patient with a history of alcoholic cirrhosis who developed SBP and concurrent bacteremia with the anaerobe Clostridium tertium. The patient was successfully treated with intravenous antibiotics and was discharged home on oral ciprofloxacin. This case report is unique in that it is the fourth documented Clostridium tertium SBP case, utilized MALDI-TOF mass spectrometry for organism identification, and susceptibility testing for select antibiotics was performed.

Ertapenem-Induced Encephalopathy in a Patient With Normal Renal Function.

Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem. Encephalopathy is a type of neurotoxicity that is defined as a diffuse disease of the brain that alters brain function or structure. We report a patient with normal renal function who developed ertapenem-induced encephalopathy manifesting as altered mental status, hallucinations, and dystonic symptoms. The patient's symptoms improved dramatically following ertapenem discontinuation, consistent with case reports describing ertapenem neurotoxicity in renal dysfunction. Since clinical evidence strongly suggested ertapenem causality, we utilized the Naranjo Scale to estimate the probability of an adverse drug reaction to ertapenem. Our patient received a Naranjo Scale score of 7, suggesting a probable adverse drug reaction, with a reasonable temporal sequence to support our conclusion.

The South Carolina rural-urban HIV continuum of care.

The HIV continuum of care model is widely used by various agencies to describe the HIV epidemic in stages from diagnosis through to virologic suppression. It identifies the various points at which persons living with HIV (PLWHIV) within a population fail to reach their next step in HIV care. The rural population in the Southern United States is disproportionally affected by the HIV epidemic. The purpose of this study was to examine these rural-urban disparities using the HIV care continuum model and determine at what stages these differences become apparent. PLWHIV aged 13 years and older in South Carolina (SC) were identified using data from the enhanced HIV/AIDS Reporting System. The percentages of PLWHIV linked to care, retained in care, and virologically suppressed were determined. Rural versus urban residence was determined using the Office of Management and Budget classification. There were 14,523 PLWHIV in SC at the end of 2012; 11,193 (77%) of whom were categorized as urban and 3305 (22%) as rural. There was no difference between urban and rural for those who had received any care: 64% versus 64% (p = .61); retention in care 53% versus 53% (p = .71); and virologic suppression 49% versus 48% (p = .35), respectively. The SC rural-urban HIV cascade represents the first published cascade of care model using rural versus urban residence. Although significant health care disparities exist between rural and urban residents, there were no major differences between rural and urban residents at the various stages of engagement in HIV care using the HIV continuum of care model.

Non-tuberculous mycobacterial bloodstream infections in patients with indwelling vascular catheters - the role of sickle cell anaemia.

INTRODUCTION: Few studies have examined risk factors for nontuberculous mycobacteria (NTM) bloodstream infections (BSI) involving indwelling vascular catheters (IDVC). Sickle cell anaemia (HbSS/SC) is known to affect several aspects of the immune system leading to relative immune deficiency. The purpose of this retrospective nested case-control study was to determine if HbSS/SC is a risk factor for NTM BSI among individuals with IDVCs. METHODS: All NTM IDVC infections (cases) at two tertiary hospitals from 2008 to 2014 were reviewed. Cases were matched 2:1 with controls who had IDVC infections due to organisms other than NTM. Matching criteria included age within 10 years and IDVC infection within three months of index case. Logistic regression was used to identify risk factors for IDVC infection due to NTM. RESULTS: Nineteen NTM BSIs were identified. Three cases were excluded because they did not have IDVCs at the time their BSI was identified. Sixteen cases of NTM IDVC infection were matched to 32 controls with IDVC infections due to other organisms. The mean age of patients with IDVC infections was 48.5 years and 28 (58%) were male. Compared to the control group those with NTM BSI were more likely to have HbSS/SC 38% (6/16) versus 6% (2/32) (p = .006). CONCLUSION: IDVCs are a risk factor for NTM BSI. Sickle cell anaemia appears to be a risk factor for IDVC infections due to NTM. This study is limited by the small sample size. A larger study is needed to further investigate the association between HbSS/SC and NTM IDVC infections.

The South Carolina HIV Cascade of Care.

OBJECTIVES: In recent years, the human immunodeficiency virus (HIV) cascade of care describing the spectrum of engagement in HIV care from diagnosis to virologic suppression has been used widely in determining the progress and success in public health efforts to control the HIV epidemic. For more than a decade South Carolina consistently ranked among the top10 states in the United States with the highest acquired immunodeficiency syndrome case rates, suggesting late diagnoses and issues with retention in care. The primary objective of this study was to develop an HIV cascade of care for the state that may help identify opportunities for appropriate future interventions. METHODS: The South Carolina Enhanced HIV/AIDS Reporting System database was used to develop the HIV cascade of care indicating the percentages of the diagnosed individuals who were linked to care, received any care, were retained in care, and achieved virologic suppression using standardized metrics recommended by the Centers for Disease Control and Prevention. The sample included all individuals in South Carolina who were diagnosed as having HIV by December 31, 2011 and who were alive at the end of 2012. RESULTS: Of the 14,523 South Carolinians living with HIV at the end of 2012, 64% had received any HIV care, 53% were retained in care, and 48% were virologically suppressed during 2012. CONCLUSIONS: This is the first HIV cascade of care model for South Carolina. Efforts are needed to improve public health initiatives to link, engage, and retain individuals with HIV in care.