Sadaf Aslam

Metabolomics Reveals Attenuation of the SLC6A20 Kidney Transporter in Nonhuman Primate and Mouse Models of Type 2 Diabetes Mellitus

To enhance understanding of the metabolic indicators of type 2 diabetes mellitus (T2DM) disease pathogenesis and progression, the urinary metabolomes of well characterized rhesus macaques (normal or spontaneously and naturally diabetic) were examined. High-resolution ultra-performance liquid chromatography coupled with the accurate mass determination of time-of-flight mass spectrometry was used to analyze spot urine samples from normal (n = 10) and T2DM (n = 11) male monkeys. The machine-learning algorithm random forests classified urine samples as either from normal or T2DM monkeys. The metabolites important for developing the classifier were further examined for their biological significance. Random forests models had a misclassification error of less than 5%. Metabolites were identified based on accurate masses (<10 ppm) and confirmed by tandem mass spectrometry of authentic compounds. Urinary compounds significantly increased (p < 0.05) in the T2DM when compared with the normal group included glycine betaine (9-fold), citric acid (2.8-fold), kynurenic acid (1.8-fold), glucose (68-fold), and pipecolic acid (6.5-fold). When compared with the conventional definition of T2DM, the metabolites were also useful in defining the T2DM condition, and the urinary elevations in glycine betaine and pipecolic acid (as well as proline) indicated defective re-absorption in the kidney proximal tubules by SLC6A20, a Na+-dependent transporter. The mRNA levels of SLC6A20 were significantly reduced in the kidneys of monkeys with T2DM. These observations were validated in the db/db mouse model of T2DM. This study provides convincing evidence of the power of metabolomics for identifying functional changes at many levels in the omics pipeline.

Formulating a researchable question: a critical step for facilitating good clinical research.

Developing a researchable question is one of the challenging tasks a researcher encounters when initiating a project. Both, unanswered issues in current clinical practice or when experiences dictate alternative therapies may provoke an investigator to formulate a clinical research question. This article will assist researchers by providing step-by-step guidance on the formulation of a research question. This paper also describes PICO (population, intervention, control, and outcomes) criteria in framing a research question. Finally, we also assess the characteristics of a research question in the context of initiating a research project.

Pharmacist Advancement of Transitions of Care to Home (PATCH) Service.

Background There is a paucity of literature on a well-defined role of a pharmacist in different aspects of transition of care service (TCS). Although health care institutions have specific details on the discharge process, there is a need for a sustainable TCS with a well-defined role of pharmacists. Objective To describe the impact of a pharmacist-led TCS on acute health care utilization, clinic quality indicators, and identification and resolution of medication-related problems (MRPs). Methods A pharmacist-managed TCS service, referred to as the Pharmacist Advancement of Transitions of Care to Home (PATCH) service, was established at an academic medical center, where high-risk patients received a postdischarge phone call from a pharmacist followed by a face-to-face meeting with the pharmacist and the patients primary care provider (PCP). In a prospective transitions of care group (n = 74), outcomes of patients such as acute health care utilization (an emergency department visit or an inpatient readmission, within 30 days post discharge), clinic quality indicators, and identification and resolution of MRPs were compared to a retrospective control group (n = 87) who received the standard of care. Results Utilization of acute health care services was significantly lower in the prospective group compared to the retrospective control group (23% vs 41.4%; P = .013). A total of 49 MRPs were discovered in patients who received the TCS. Conclusions Pharmacists play an integral role in improving the transitions of care to reduce acute health care utilization. In addition, they may improve care transitions by optimizing clinic quality indicators and by identifying and resolving MRPs.

Matching research design to clinical research questions

The importance of randomized controlled trials (RCTs) versus observational studies has been debated for several years. However, the question is not whether RCTs are better than observational study designs. RCTs certainly provide the most unbiased answers in scenarios where it is logistically and ethically feasible to conduct both RCTs and observational studies. That is, study design is not a choice but a function of matching the research question to provide the most unbiased answers. The basic concept that underpins every clinical research project is the requirement of a clearly defined research question domain. Broadly, the clinical research question domain relates to prognosis, diagnostic accuracy, treatment or adverse events. While RCTs provide the most unbiased answers on questions related to the efficacy of treatments, other designs are better suited to answer questions related to prognosis or diagnostic accuracy of tests. In this paper, we illustrate the significance of matching study design to the research question domain while using clinical scenarios as an example. Although there are several other question domains that also concern the practice of medicine, we are only focusing on study designs concerning the issue of prognosis and diagnostic accuracy in this paper.

Two cases of disseminated infection following live organism anti-cancer vaccine administration in cancer patients

Vaccines containing live attenuated bacterial or viral organisms are currently being investigated as potential therapy for locally advanced or metastatic cancers. However, the use of such live organisms in an immunocompromised population, such as patients who recently or are currently receiving chemotherapy, raises the concern that these organisms can themselves disseminate and cause frank infection. We report a hereunto unreported phenomenon of anti-cancer vaccines (containing live attenuated organisms) leading to frank, disseminated infection. We submit that occurrence of this phenomenon must be watched for by all members of the interdisciplinary cancer treatment team.

Essentials of Genomics in the Continuum of Translational Research

New developments in the genomics field have led to increasing expectations for its impact on clinical practice and disease prevention. There is a need to develop comprehensive research guidelines so that human genome discoveries can be translated into health practice. This should be done in a way that maximizes health benefits and minimizes harm to individuals and populations.

Outcomes of abdominal surgeries in cirrhotic patients performed by liver transplant surgeons: Are these safe?

BACKGROUND Elective abdominal surgeries in patients with cirrhosis have been discouraged due to the high risk of complications. This study investigates the outcomes and safety of surgeries for hernias, and laparoscopic cholecystectomies in cirrhotic patients. METHODS A retrospective cohort study that compared 91 cirrhotic patients to a control group of non-cirrhotic patients operated by liver transplant surgeons was conducted between 2009 and 2015. RESULTS No statistical significance found in re-admission rates or complication rates (p = 0.21). Hernia recurrent rates were similar (p = 0.27). Survival rates among cirrhotic versus non cirrhotic group was 93.4% and 98.9% respectively (p = 0.0539). Amongst the 91 cirrhotic patients, there was a 100% survival rate for both ventral herniorrhaphies and laparoscopic cholecystectomy. Survival in umbilical and inguinal herniorrhaphies was 88.2% and 89.5% respectively. Mortality rate for umbilical and inguinal hernias was 11.7% and10.5% respectively. Mortality by Child-Pugh (CP) class were; 8.8% for CP B and 10.7% for CP class C. All CP class A patients survived. CONCLUSIONS Our study indicates that elective operations could be performed safely with acceptable mortality in cirrhotic patients.