Using bacteria to target cancer cells

I’ve been studying for Step 1 (boards at the end of the 2nd year of med school) and ran across tumor suppressor genes (TSGs). These are genes that serve important functions in preventing cancer. When you lose function or expression of both alleles (the 2 copies of a gene) of a tumor suppressor gene in a cell, cancer risk increase.

Think of it as what happens to a yard in front on an abandoned house: The weeds start to grow out of control.

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The structure of retinoblastoma protein (Rb1) from Uniprot

A specific gene , Rb (Retinoblastoma), is responsible for inhibiting a transcription factor called E2F. This is a fancy way of saying that Rb blocks the function of another protein, one that allows the cell to grow. When Rb works properly, a cell stops growing. When Rb doesn’t, the cell keeps growing regardless of any stop signs from the environment or internal conditions. This loss of Rb function causes cancers such as osteosarcoma and retinoblastoma.

This same mechanism, inhibition of E2F, is shared by a few infectious diseases that make people very sick. These diseases include Corynebacteria diptheria (Diptheria), Vibrio cholerae (Cholera), Pseudomonas aeruginosa (Common cause of hospital-acquired infections), and Bordatella pertussis (Whooping cough).

This is pretty interesting. Why? These bacteria could potentially be used as vectors for anti-cancer therapy.  Could we use modified, non-virulent strains of these bacteria to target cancer cells with insufficient Rb signaling?

Infectious diseases that cause cancer (Oncogenic infectious diseases)

VIRAL (Oncoviruses)

HPV – Cervical cancer (Esp HPV 16, 18, 33, 35)

HHV-4/ EBV: Nasopharyngeal carcinoma, Burkitt’s lymphoma

HHV-8 -Kaposi Sarcoma

HTLV-1: ATLL (Adult T-cell leukemia)

HBV/ HCV: HCC (Hepatocellular carcinoma)

Merkel cell polyomavirus: Merkell cell lyphoma

BACTERIAL (Oncobacteria)

H. pylori: MALT (Gastrointestinal mucosal lymphoma)

Bartonella henselae: Bacillary angiomatosis (vascular granulomatous tumors)

 

Hands on: IT training for medical students

There’s one thing doctors are expected to do best: Provide exceptional care to each patient. This expectation includes good health outcomes, guarding a patient against preventable disease, and even protecting a community from disease.  The use of information technology is often an important component of delivering high-quality care and optimizing patient outcomes. Medical practices that leverage IT tools, such as electronic health records and billing systems, are able to engage patients in their healthcare at higher levels, improve outcomes, and improve provider productivity. Both patients and healthcare practices experience benefits when IT tools are used effectively.

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Using an IT tool well requires one thing: Knowing how to use it. Many healthcare providers use electronic health records, billing and administrative systems, and their own email on a daily basis, but few feel comfortable with IT tools. In fact, fewer than 50% of doctors use electronic records at all in clinical practice. Focused IT training specifically for IT use in healthcare can make these tools easier and more accessible to health care professionals. Becoming more familiar with IT could also encourage more health care providers to engage in designing better tools. Improving the way health care professionals use IT starts with educating health care students to become proficient IT users.

Students at the University of Kansas School of Medicine (KU Med) use IT tools to study and share materials. We already know how to use some tools well and integrate them into our workflow. For instance, the 2nd year class uses a group page on Facebook to share study materials, news and events affecting the class, and to collaborate on assignments. Tools that would accomplish these same tasks and offered by KU Med, such as SharePoint and Lync, are rarely used. When time and resources are limited, students will use the tools most familiar and easy to use.

We can improve student IT use through training. Some resources already exist on campus, including training done by the campus library. Alongside these resources, we need to develop easy and accessible IT training that specifically focuses on health professional student needs. The more comfortable health care students are with using IT, the better equipped they will be to use health IT for its intended purpose as professionals: Providing exceptional care to each patient.

Displair and visual tech for health at a distance

When a doctor is far from a patient how do the two interact?

Digital tech enables a doctor to see a patient even when they’re far apart. Care at a distance can be termed telemedecine, telehealth, mobile health, and others, and all refer to health care beyond in-person delivery.

Is a visit over Skype or WebRTC enough to achieve enough information sharing for an effective appointment? Is it enough to triage a situation, for instance to assess whether a 5-year old girl with a cough at 8pm and concerned parents needs to visit a clinic the next morning or not? It is definitely enough to simply check in with someone, which can be an extremely effective method of follow-up in encouraging patient adherence and healthy behaviors.

Do tools like Displair only improve visits incrementally or could they significantly change how patients and health care providers interact at a distance? Would this technology make complicated assessments  possible?

New cardiovascular drug for heart attack patients

New cardiovascular drug for heart attack patients

The FDA just overwhelmingly approved a new drug, Vorapaxar, for heart attack patients. Vorapaxar appears effective in the acute setting in reducing the risk of poor outcomes such as another heart attack, stroke and death. Many medications including Melagatran, Hirudin, and Heparin also inhibit thrombin, the target of Vorapaxar in preventing clot formation.

The wild thing is the numbers: It would take treating 1000 patients with Vorapaxar to have a positive effect on 1 patient. The risk of studied complications, such as stroke and death, drops significantly by 13% in treated patients, but comes with a rise in bleeding risk. There’s a trade-off because we have not yet developed medications that target heart attack mechanisms only without extended side effects. Can you make a thrombin inhibitor effective within a patient-specific range to be effective at preventing clots without the bleed risk? This would likely require metrics on individual platelet activity and coagulation, including a bioniformatics panel to monitor and predict genomic and proteomic activity.

Cool band name: The biometric monitors and 30-day readmission risk

What do Jawbone Up, Nike Fuelband, Fitbit, Larklife, and many other monitors have in common? These health monitors could be used to track people for specific health outcomes, like 30-day hospital readmission rates.

Thanks for the image to FitSugar

Thanks for the image to FitSugar

Since the passage of the ACA (Affordable Care Act) in 2010, hospital reimbursement is now tied to quality metrics including the 30-day readmission rate.  Here’s how the ACA puts money and policy on the table to lower readmission rates:

  • Section 1001, Amendment to PHSA Sec 2717(a): Hospital readmissions are a measure of quality and must be reported for reimbursement for hospital discharges.
  • Section 1331(g): Market-based incentives and reimbursement payment structures should incorporate hospital readmission rates
  • Sec 2703: Healthcare providers for Medicare enrollees with chronic conditions are reimbursed based on prevention of avoidable hospital readmissions.
  • Sec 3011:The National Strategy on Improvements in Health Care includes reducing the number of readmissions as a benchmark
  • Sec 3023: The National pilot on payment bundling includes the 30-day post-discharge period in the definition of an episode of care, meaning that health care providers are responsible for patients during this entire time. Readmission rates impact potential reimbursement.
  • Sec 3024: The Independence at Home Demo program includes the goal of lowering readmission rates with funding of $5M until 2015.
  • Section 3025: An entire program is dedicated to preventing readmissions: The Hospital Readmission Reduction Program. This section establishes an adjusted payment per discharge that penalizes the healthcare provider for a readmission within 30 days. It also includes multiple readmissions in the definition of high-risk patients that require more resources. $500 million is allocated to the Centers for Medicare & Medicaid Services through 2015 for this program.

The calculated reimbursement based on DRG (diagnosis-related group):

 Payment = Base DRG * Adjustment factor

                 What is the Adjustment factor? 1-Excess readmission ratio

                       What is Excess readmission ratio? Aggregate pay for excess readmits: For all discharges

  • Sections 3501, 399 (PHSA): Health care delivery systems research specifically focuses on reducing preventable readmissions.

Readmissions are now a huge factor in healthcare provider reimbursement and other financial incentives. Lower readmission rates signal lower long-term healthcare costs and potentially better health outcomes for patients. All of this means means we should be focusing on tools and methods to help us lower patient readmissions.

What if we try using biometric trackers such as Jawbone Up, Fitbit, and others to help a group of patients stay healthy enough to avoid a readmission? Could biometric tracking help improve patient outcomes and make economic sense for healthcare providers?