Key challenges in bringing CRISPR-mediated somatic cell therapy into the clinic.

Genome editing using clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated proteins offers the potential to facilitate safe and effective treatment of genetic diseases refractory to other types of intervention. Here, we identify some of the major challenges for clinicians, regulators, and human research ethics committees in the clinical translation of CRISPR-mediated somatic cell therapy.

Sound understanding of environmental, health and safety, clinical, and market aspects is imperative to clinical translation of nanomedicines.

Nanotechnology has transformed materials engineering. However, despite much excitement in the scientific community, translation of nanotechnology-based developments has suffered from significant translational gaps, particularly in the field of biomedicine. Of the many concepts investigated, very few have entered routine clinical application. Safety concerns and associated socioeconomic uncertainties, together with the lack of incentives for technology transfer, are undoubtedly imposing significant hurdles to effective clinical translation of potentially game-changing developments. Commercialisation aspects are only rarely considered in the early stages and in many cases, the market is not identified early on in the process, hence precluding market-oriented development. However, methodologies and in-depth understanding of mechanistic processes existing in the environmental, health and safety (EHS) community could be leveraged to accelerate translation. Here, we discuss the most important stepping stones for (nano)medicine development along with a number of suggestions to facilitate future translation.

Yearly Clinical Laboratory Test Expenditures for Different Medical Specialties in a Major Canadian City.

OBJECTIVES: Very little is known about the relative contributions of physician specialty groups and individual physicians to overall clinical laboratory expenditures. The objectives of this study were to determine the costs of clinical laboratory test expenditures attributable to 30 medical specialties and the associated per capita physician expenditures for an entire major Canadian city. Only chemistry, hematology, and microbiology tests were included in this study. METHODS: Retrospective cohort study involving all physicians in Calgary, Canada, and surrounding areas (n = 3,499) and secondary data on laboratory test orders. RESULTS: Data were obtained on approximately 20 million test requests. The mean clinical laboratory test expenditure, in Canadian dollars, per physician was $27,945 for all physicians combined. Total expenditures by primary care physicians (family physicians and general practitioners) accounted for 58% of total expenditures. CONCLUSIONS: There was wide variation in clinical laboratory test expenditures among specialties and on a per capita basis within medical specialties.

Anatomy of a value proposition for laboratory medicine.

Value is now becoming a key driver in the ongoing development of healthcare delivery; key facets include the identification of what is valuable and how that value can be identified, leveraged, and delivered. The concept of a value proposition is widely used in business but can be used in healthcare as a statement of the benefits, costs and value that an organization can deliver to its customers. The foundation of this statement in laboratory medicine is evidence of clinical and cost effectiveness, not only for the patient, but also for other stakeholders involved in the delivery of healthcare, e.g., the carer, service provider, commissioner, purchaser, and the supplier of the test or device, as well as society as a whole. However the value of any laboratory medicine investigation is only achieved if the output (the test result(s)), is acted upon by the initiator of the investigation. Laboratory medicine is one part of a complex intervention, and so the value proposition should encompass the breadth of that intervention - from addressing the unmet need through the generation of clinical, operational and economic outcomes. A value proposition in laboratory medicine is central to successful innovation and quality improvement in healthcare.

National epilepsy surgery program: realistic goals and pragmatic solutions.

There are multiple social, economic, and medical challenges in establishing successful epilepsy surgery programs in India and in other low- and middle-income countries (LAMIC). These can be overcome by reproducing pragmatic and proven epilepsy surgery models throughout the country with a larger aim of developing a national epilepsy surgery program so as to provide affordable and quality surgical care to all the deserving patients. An organized national epilepsy surgery support activity can help interested centers in India and in neighboring countries in developing epilepsy surgery programs.

Monitoring of HIV viral load, CD4 cell count, and clinical assessment versus clinical monitoring alone for antiretroviral therapy in low-resource settings (Stratall ANRS 12110/ESTHER): a cost-effectiveness analysis.

BACKGROUND: In low-income countries, the use of laboratory monitoring of patients taking antiretroviral therapy (ART) remains controversial in view of persistent resource constraints. The Stratall trial did not show that clinical monitoring alone was non-inferior to laboratory and clinical monitoring in terms of immunological recovery. We aimed to evaluate the costs and cost-effectiveness of the ART monitoring approaches assessed in the Stratall trial. METHODS: The randomised, controlled, non-inferiority Stratall trial was done in a decentralised setting in Cameroon. Between May 23, 2006, and Jan 31, 2008, ART-naive adults were randomly assigned (1:1) to clinical monitoring (CLIN) or viral load and CD4 cell count plus clinical monitoring (LAB) and followed up for 24 months. We calculated costs, number of life-years saved (LYS), and incremental cost-effectiveness ratios (ICERs) with data from patients who had been followed up for at least 6 months. We considered two cost scenarios in which viral load plus CD4 cell count tests cost either US$95 (scenario 1; Abbott RealTime HIV-1 assay) or $63 (scenario 2; generic assay). We compared ICERs with a WHO-recommended threshold of three times the per-person gross domestic product (GDP) for Cameroon ($3670-3800) and an alternative lower threshold of $2385 to determine cost-effectiveness. We assessed uncertainty with one-way sensitivity analyses and cost-effectiveness acceptability curves. FINDINGS: 188 participants who underwent LAB and 197 who underwent CLIN were followed up for at least 6 months. In scenario 1, LAB increased costs by a mean of $489 (SD 430) per patient and saved 0·103 life-years compared with CLIN (ICER of $4768 [95% CI 3926-5613] per LYS). In scenario 2, the incremental mean cost of LAB was $343 (SD 425) -ie, an ICER of $3339 (2507-4173) per LYS. A combined strategy in which LAB would only be used in patients starting ART with a CD4 count of 200 cells per µL or fewer suggests that 0·120 life-years would be saved at an additional cost of $259 per patient in scenario 1 (ICER of $2167 [95% CI 1314-3020] per LYS) and $181 in scenario 2 (ICER of $1510 [692-2329] per LYS) when compared with CLIN. INTERPRETATION: Laboratory monitoring was not cost effective in 2006-10 compared with clinical monitoring when the Abbott RealTime HIV-1 assay was used according to the $3670 cost-effectiveness threshold (three times per-person GDP in Cameroon), but it might be cost effective if a generic in-house assay is used. FUNDING: French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER).

The Hippocratic oath: a comparative analysis of the ancient text's relevance to American and Indian modern medicine.

Hippocrates (460-375 B.C.), an ancient Greek physician considered the "Father of Medicine," constructed the groundwork for the principles of ethics in medicine over 2,500 years ago in his establishment of the Hippocratic Oath. One of the oldest binding documents in history, the text has remained the ethical template for physicians to this day. The changing cultural and social environment of modern society, accompanied by the advancement in scientific knowledge and therapeutic tools, has surfaced the need to reframe ethical perspective in modern medicine. Progress in aspects such as organ transplantation, stem cell technology, and genetic engineering has welcomed a new set of ethical dilemmas. These dilemmas have become intimately intertwined with the impact of commercialization, as seen by the interplay between legislation, health care, and pharmaceutical businesses. This paper seeks to dissect the principles of the original Hippocratic Oath and analyze the template in relation to the ethical dilemmas presented by contemporary medicine. Examination will provide a deeper understanding of the paradigm shift in modern medical ethics. Both the value of the Oath and the level of awareness of modern ethical dilemmas through the lens of American and Indian medical graduates will be assessed.

Establishing an academic neurology specialty program: experiences over a five-year period.

Veterinary neurology is an expanding specialty field. At the time of this writing, 13 out of 33 (40%) US and Canadian veterinary colleges, and many more veterinary colleges outside of North America, had no active clinical neurology service. New academic programs will likely be established to fill this need, often starting with a single neurologist. Establishing a neurology service with one founding faculty member can be accomplished by developing the program in phases and creating a support network that optimizes faculty strengths and interests. Such an approach allows for the gradual expansion of services and staffing in a manageable way to ultimately provide a full-service program. A description of this development process at Purdue University School of Veterinary Medicine is presented as a case study and model for the establishment of other neurology or specialty services.

The ethics and reality of rationing in medicine.

Rationing is the allocation of scarce resources, which in health care necessarily entails withholding potentially beneficial treatments from some individuals. Rationing is unavoidable because need is limitless and resources are not. How rationing occurs is important because it not only affects individual lives but also expresses society's most important values. This article discusses the following topics: (1) the inevitability of rationing of social goods, including medical care; (2) types of rationing; (3) ethical principles and procedures for fair allocation; and (4) whether rationing ICU care to those near the end of life would result in substantial cost savings.

Comparison of Swiss basic health insurance costs of complementary and conventional medicine.

BACKGROUND: From 1999 to 2005, 5 methods of complementary and alternative medicine (CAM) applied by physicians were provisionally included into mandatory Swiss basic health insurance. Between 2012 and 2017, this will be the case again. Within this process, an evaluation of cost-effectiveness is required. The goal of this study is to compare practice costs of physicians applying CAM with those of physicians applying solely conventional medicine (COM). METHODS: The study was designed as a cross-sectional investigation of claims data of mandatory health insurance. For the years 2002 and 2003, practice costs of 562 primary care physicians with and without a certificate for CAM were analyzed and compared with patient-reported outcomes. Linear models were used to obtain estimates of practice costs controlling for different patient populations and structural characteristics of practices across CAM and COM. RESULTS: Statistical procedures show similar total practice costs for CAM and COM, with the exception of homeopathy with 15.4% lower costs than COM. Furthermore, there were significant differences between CAM and COM in cost structure especially for the ratio between costs for consultations and costs for medication at the expense of basic health insurance. Patients reported better quality of the patient-physician relationship and fewer adverse side effects in CAM; higher cost-effectiveness for CAM can be deduced from this perspective. CONCLUSION: This study uses a health system perspective and demonstrates at least equal or better cost-effectiveness of CAM in the setting of Swiss ambulatory care. CAM can therefore be seen as a valid complement to COM within Swiss health care.

A national cohort study of MD-PhD graduates of medical schools with and without funding from the National Institute of General Medical Sciences' Medical Scientist Training Program.

PURPOSE: To determine whether prematriculation characteristics and career-setting preferences of MD-PhD graduates differ according to their schools' funding from the National Institute of General Medical Sciences' Medical Scientist Training Program (MSTP). METHOD: The Association of American Medical Colleges provided deidentified records for the national cohort of all 1993-2000 U.S. medical school matriculants, 3,180 of whom graduated with dual MD-PhD degrees by March 2, 2009. The authors examined prematriculation characteristics, educational outcomes, and career-setting preferences at graduation in association with MD-PhD program graduation from schools with long-standing MSTP-funded, recent MSTP-funded, and non-MSTP-funded programs. RESULTS: Of 3,142 MD-PhD graduates with prematriculation data, 30% were women and 36% were nonwhite. Graduates from long-standing MSTP-funded schools (63% of 3,142 graduates) composed a more highly selective group academically (based on Medical College Admission Test scores) than did graduates from recent MSTP-funded (6%) and non-MSTP-funded schools (31%). Women and nonwhite graduates were more likely to have graduated from long-standing MSTP-funded schools. Controlling for MSTP funding and other variables, graduates with total debt of $100,000 or more were more likely to indicate non-research-related career-setting preferences (nonuniversity clinical practice: odds ratio [OR] 3.58, 95% confidence interval [CI] 1.86-6.87; undecided/other: OR 2.15, 95% CI 1.29-3.60). Neither gender nor race/ethnicity was independently associated with graduates' career-setting preferences. CONCLUSIONS: Women and nonwhite MD-PhD graduates more likely graduated from long-standing MSTP than non-MSTP-funded schools. Controlling for institutional MSTP funding, MD-PhD graduates with high debt were more likely to indicate non-research-related career-setting preferences.