Naveen Patil

Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management

Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (http://www.diabetesatlas.org/). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas. T2DM is a major contributor to the very large rise in the rate of non-communicable diseases affecting developed as well as developing nations. In this mini review, we endeavor to outline the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM.

HIV-Associated TB Syndemic: A Growing Clinical Challenge Worldwide.

The association of tuberculosis (TB) with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome over the past several years has become an emerging syndemic. Approximately 10% of people living with HIV (PLHIV) with latent TB infection will develop active TB disease each year. In this review, we highlight that this phenomenon is not limited to high endemic regions, such as Afro-Asian nations, but globalization/migration is causing increased case detection even in developed nations, such as the United States. Active screening should be performed for TB in PLHIV. A high degree of clinical suspicion for TB is warranted in PLHIV presenting with fever, cough, and unintentional weight loss. HIV–Mycobacterium tuberculosis (MTB) coinfection is often paucibacillary, precluding diagnosis by conventional diagnostics and/or smear microscopy/culture. Improved detection of pulmonary and extrapulmonary TB is now possible by incorporation of the GeneXPERT MTB/RIF assay (Cepheid Inc., Sunnyvale, CA, USA). The World Health Organization recommends instituting immediate therapy for MTB, in conjunction with ongoing or newly introduced anti-retroviral therapy. Vigilance is required to detect drug-induced organ injuries, and early-treatment-induced immune reconstitution inflammatory syndrome. Collaborating MTB and HIV activities in concentrated HIV epidemic settings should become a high public health priority.

The Road to Tuberculosis (Mycobacterium tuberculosis) Elimination in Arkansas; a Re-Examination of Risk Groups

Objectives This study was conducted to generate knowledge useful for developing public health interventions for more effective tuberculosis control in Arkansas. Methods The study population included 429 culture-confirmed reported cases (January 1, 2004–December 31, 2010). Mycobacterium tuberculosis genotyping data were used to identify cases likely due to recent transmission (clustered) versus reactivation (non-clustered). Poisson regression models estimated average decline rate in incidence over time and assessed the significance of differences between subpopulations. A multinomial logistic model examined differences between clustered and non-clustered incidence. Results A significant average annual percent decline was found for the overall incidence of culture-confirmed (9%; 95% CI: 5.5%, 16.9%), clustered (6%; 95% CI: 0.5%, 11.6%), and non-clustered tuberculosis cases (12%; 95% CI: 7.6%, 15.9%). However, declines varied among demographic groups. Significant declines in clustered incidence were only observed in males, non-Hispanic blacks, 65 years and older, and the rural population. Conclusions These findings suggest that the Arkansas tuberculosis control program must target both traditional and non-traditional risk groups for successful tuberculosis elimination. The present study also demonstrates that a thorough analysis of TB trends in different population subgroups of a given geographic region or state can lead to the identification of non-traditional risk factors for TB transmission. Similar studies in other low incidence populations would provide beneficial data for how to control and eventually eliminate TB in the U.S.

High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection

Background Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Initial experience with GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control Program.

BACKGROUND Mycobacterium tuberculosis remains one of the most significant causes of death from an infectious agent. Rapid and accurate diagnosis of pulmonary and extra-pulmonary tuberculosis (TB) is still a great challenge. The GeneXpert MTB/RIF assay is a novel integrated diagnostic system for the diagnosis of tuberculosis and rapid detection of Rifampin (RIF) resistance in clinical specimens. In 2012, the Arkansas Tuberculosis Control Program introduced GeneXpert MTB/RIF assay to replace the labour-intensive Mycobacterium Tuberculosis Direct (MTD) assay. AIMS To rapidly diagnose TB within two hours and to simultaneously detect RIF resistance. OBJECTIVES Describe the procedure used to introduce GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control Program.Characterise the current gap in rapid M. tuberculosis diagnosis in Arkansas.Assess factors that predict acid fast bacilli (AFB) smearnegative but culture-positive cases in Arkansas.Illustrate, with two case reports, the role of GeneXpert MTB/RIF assay in reduction of time to confirmation of M. tuberculosis diagnosis in the first year of implementation. METHOD Between June 2012 and June 2013, all AFB sputum smearpositive cases and any others, on request by the physician, had GeneXpert MTB/RIF assay performed as well as traditional M. tuberculosis culture and susceptibilities using Mycobacteria Growth Indicator Tube (MGIT) 960 and Löwenstein-Jensen (LJ) slants. Surveillance data for January 2009-June 2013 was analysed to characterise sputum smear-negative but culture-positive cases. RESULTS Seventy-one TB cases were reported from June 2012- June 2013. GeneXpert MTB/RIF assay identified all culture-positive cases as well as three cases that were negative on culture. Also, this rapid assay identified all six smear-negative but M. tuberculosis culture-positive cases; two of these cases are described as case reports. CONCLUSION GeneXpert MTB/RIF assay has made rapid TB diagnosis possible, with tremendous potential in determining isolation of TB suspects on one hand, and quickly ruling out TB whenever suspected.

Pulmonary Tuberculosis in a Patient with Cystic Fibrosis

Context: Mycobacterium tuberculosis (MTB) infection is rarely seen in cystic fibrosis (CF) patients. Case Report: We report a 24-year-old CF patient with fever, cough, hemoptysis, and weight loss of 1week duration prior to admission. Past sputum cultures grew methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. The patient was treated with broad spectrum antibiotics based on previous culture data, but failed to improve. Chest radiograph and computed tomography (CT) chest revealed chronic collapse of the anterior subsegment of right upper lobe and multiple bilateral cavitary lesions which were worse compared to prior films. MTB was suspected and was confirmed by positive acid-fast bacilli (AFB) smears and cultures. After receiving first-line antituberculous drugs, the patient′s condition markedly improved. Conclusion: MTB is an infrequent finding, but considered a potential pathogen in CF patients, and may lead to serious pulmonary complications if there is a delay in diagnosis and treatment.

Rifampicin-induced nephrotoxicity in a tuberculosis patient

Rifampicin is a widely used anti-tuberculosis agent. On rare occasions, the drug can cause adverse effects such as acute renal failure, though most regain complete renal function upon discontinuation of therapy. The following case report describes a 38 year old Hispanic male presenting with pulmonary tuberculosis who developed rifampicin-induced renal toxicity. He recovered renal function upon discontinuation of the medication without the use of corticosteroids.

Tuberculosis reinfection in a pregnant cystic fibrosis patient

Cystic Fibrosis (CF) is a multisystem disease predominantly affecting the airways and predisposing patients to recurrent infections with various multidrug resistant organisms. Mycobacterium tuberculosis (MTB) infection is rarely seen, but considered a potential pathogen in CF patients. We report a 26 year old pregnant CF patient on Ivacaftor who was admitted with symptoms suggestive of tuberculosis. Three years prior to the current admission, she had completed four drug anti- MTB therapy for pulmonary tuberculosis and was considered cured as her sputum cultures after six months of treatment were negative. Genotype analysis revealed the current MTB strain to be different from the strain causing the previous infection. After receiving first line anti-tuberculous regimen for nine months, the patients condition markedly improved culminating in an uneventful pregnancy and delivery. To our knowledge, this is the only reported case of reinfection tuberculosis in a CF patient.

Mycobacterium tuberculosis infection in a HIV-positive patient

Mycobacterium tuberculosis (MTB) and human immunodeficiency virus (HIV) coinfection remains a global public health challenge. We report a 40 year old African American male who is a known HIV-positive patient, non-compliant with his antiretrovirals and developed pulmonary tuberculosis. His chief complaints were chronic cough, fever, night sweats and undocumented weight loss. He had a prior positive T-SPOT-TB test; however, chest radiograph and sputum smear examination revealed normal results. PCR-based GeneXPERT MTB/RIF assay was ordered and confirmed MTB infection. The sputum cultures grew MTB and sensitivities showed susceptibility to all primary anti-tuberculosis medications. A delay in diagnosis and initiation of MTB therapy, in the setting of HIV or AIDS, may result in rapid disease progression and worse clinical outcome.

Effectiveness of contact investigations for tuberculosis control in Arkansas.

Comprehensive assessment of the effectiveness of contact investigations for tuberculosis (TB) control is still lacking. In this study, we use a computational model, calibrated against notification data from Arkansas during the period 2001-2011, that reproduces independent data on key features of TB transmission and epidemiology. The model estimates that the Arkansas contact investigations program has avoided 18.6% (12.1-25.9%) of TB cases and 23.7% (16.4-30.6%) of TB deaths that would have occurred during 2001-2014 if passive diagnosis alone were implemented. If contacts of sputum smear-negative cases had not been included in the program, the percentage reduction would have been remarkably lower. In addition, we predict that achieving national targets for performance indicators of contact investigation programs has strong potential to further reduce TB transmission and burden. However, contact investigations are expected to have limited effectiveness on avoiding reactivation cases of latent infections over the next 60 years.