Are Primary Care Visits on the Decline?

Primary care is essential for a high-performing healthcare system, as patients with a regular primary care physician (PCP) have higher rates of recommended screenings and lower rates of preventable hospital admissions and mortality. Although recent studies suggest declining rates of primary care visits during the last decade in the United States, the contribution of practice changes, such as the use and content of such visits, to this decline is still undetermined. To address this question, researchers used nationally representative data from the National Ambulatory Medical Care Survey to analyze adult visits to PCPs and physician practice characteristics from 2007 to 2016.

The goal of a second study was to examine changes in individuals' contact with the medical system during the implementation of the Patient Protection and Affordable Care Act (ACA) within longer-term trends.

This study used data from the 2002 to 2016 Medical Expenditure Panel Survey to determine rates of contact per 1000 individuals per month for physicians, PCPs, specialty physicians, and emergency departments; inpatient hospitalizations; dental visits; and home health visits for the overall population and by age, financial status, health status, and race/ethnicity.

The number of primary care visits in the United States is unexpectedly decreasing at a time when the ACA has reduced financial barriers to care and ushered in a new era of prevention and wellness, 2 studies have found.

Experts disagree on whether this trend is good or bad for the health system. The passage of the Affordable Care Act should have increased the frequency of visits, while the use of telehealth would decrease face to face visits.  The availability of online laboratory test results obviates a clinic visit.

Other factors also changed. The length of a patient visit increased with the addition of education, coaching,  and more comprehensive visits.

In 1 study, Aarti Rao, BA, from the Icahn School of Medicine at Mount Sinai, New York City, and colleagues found that from 2008 to 2015, the average number of PCP visits per person dropped by 20% in a sample of 3.2 billion visits (−0.25 visits per person; 95% confidence interval [CI], −0.32 to −0.19). Visits dropped particularly for acute and chronic diseases, but not for general medical exams and mental illness.

Appointment Length Increased

The time of each appointment lengthened, on average, by 2.4 minutes, and each appointment addressed more concerns, enabled in part by electronic health records, and provided more preventive services and procedures, such as vaccines and wound care. In addition, appointments were less likely to have scheduled a follow-up for certain patients and conditions.

Physicians also offered much more non-face-to-face care, such as secure messaging and virtual care. For instance, it is no longer necessary in most cases for patients to come in to obtain laboratory results.

The researchers say that fewer visits can be explained partially by more comprehensive appointments and more out-of-office care.

They acknowledge, however, that the rise of high-deductible health plans may also be keeping some people from coming in at all; in addition, other factors could play a role, such as more patients seeking care at retail and urgent centers or appointments with nurse practitioners or physician assistants, which the investigators were not able to measure.

Specialist Care and Emergency Department Care Have Not Increased

The decrease in the numbers of primary care visits has not, for the most part, resulted in an increase of visits to specialists and emergency departments, Michael Johansen, MD, from Grant Medical Center, OhioHealth in Columbus, and Caroline R. Richardson, MD, from the University of Michigan, Ann Arbor, write in a second study published in the journal.[2]

In fact, the likelihood of visiting a specialist decreased for all patients younger than 65 years, Donald Pathman, MD, MPH, director of the Program on Primary Care at the University of North Carolina at Chapel Hill, explains in an accompanying editorial.[3]

That is a welcome finding, he writes, considering some "balloon" theorists have suggested when primary care visits go down, the use of more expensive care goes up.

Some changes were specific to age groups.

In this second study, emergency department visits did not change for individuals aged 18 to 40 years and those aged 65 years and older but increased for those aged 41 to 65 years.

Even though the intent of the ACA was to have a heavier primary care focus, what may be happening is that we are receiving more efficient primary care, albeit, in fewer visits, he said.

The intent of models such as accountable care organizations, he notes, is that care will be delivered and received where it is most appropriate, "and that oftentimes means you don't need an office visit," he explained.

Patients are getting more questions answered electronically, and more follow-up telephone calls are taking the place of in-office visits.

It seems the changes in the system are working in unplanned ways and most of it is good.  Perhaps we are getting more bang for ours. expensive health system.

Providers are becoming more proficient at using all the resources that have developed in IT and administrative matters.

He added that the studies show a surprising lack of response to the ACA, in that it appears the ACA did not increase the numbers of contacts with primary care or influence where people were seeking care.

In the end, neither of these studies gives a clear answer on whether less contact with primary care is a good or bad thing, Dr. Johansen explained, noting that who is not accessing primary care, where they are going instead, and how the trend affects outcomes are still unknown.









Are Primary Care Visits on the Decline?: US primary care visits are unexpectedly declining, despite the

Affordable Care Act implementation, which was intended to lower financial barriers to care and improve access to prevention and wellness.

Who Are the Key Players in Social Determinants of Health Strategy?

As healthcare organizations continue to target the social determinants of health, they must collaborate with other key players to deliver on programs.

 - The healthcare industry has come to a consensus that the social determinants of health and population health are essential considerations for delivering value-based care. But it takes a village, as the adage says, and organizations need to anticipate a number of stakeholders for making these programs a reality.

SDOH programs are inherently multi-stakeholder — they require the medical provider who will identify high-risk patients, fund sources, care coordinators or caseworkers, and the community-based partners that will help carry out interventions. Each of these stakeholders needs to be working in the same direction in order for programs to be successful.

Some hospital boards have already considered the SDH and how hospitals can effect change in SDOH for prospective patients.  The question being "Is there a return of investment? "Will this lower the direct cost of health care?

READ MORE: How Addressing Social Determinants of Health Cuts Healthcare Costs

Nutrition programs, housing initiatives, and ridesharing partnerships are some of the ways providers are reducing healthcare costs by addressing social determinants of health.

And as a fundamental part of that duty, board members are considering where to allocate financial resources to fund SDOH programming.

Adjusting Medicaid Payments for Social Determinants to Boost Care

Using a per-person adjustment for Medicaid payments to hospitals would address social determinants of health and help hospitals fund more comprehensive care, experts say. While some hospitals and organizations have outreach programs to increase accessibility for higher risk groups, this approach is to directly influence  SDH by other means. Some of these programs are already funded by other organizations, non-profits, food banks, homelessness programs. Hospitals can be a source of information as well.  Emergency room demographics reveal the data on homelessness, substandard housing, and poor nutrition. Substance abuse organizations can network with hospitals to deliver this information as well.  Emergency rooms function as social crisis centers. Public health and federally qualified health centers are organized centers of SDOH information. The information is already in place from Medicare and county hospitals.

READ MORE: How Food Security Programs Target Social Determinants of Health

How Social Risk Factors Influence Value-Based Reimbursement

The AHA (American Hospital Association) recommends that provider organizations take the following steps to implement similar housing initiatives:

Identify issues, opportunities, and risk
Establish strategic partnerships inside and beyond the hospital
Research potential interventions, such as successful programs run by other health systems
Consider funding implications and what sources are available for funding (i.e. local government and community agencies)
Educate patients, providers, and the community about the initiative
Assess and modify initiative to improve housing options, patient eligibility, and outcomes

Population health management and value-based reimbursement success hinge on reducing healthcare costs not only when a patient is in the exam room, but also when they are beyond the walls of the practice or hospital. Therefore, understanding where a patient lives, their income, education level, job status, and other social determinants of health (SDOH) is critical as providers aim to reduce healthcare costs and unnecessary utilization.

Socioeconomic factors are responsible for approximately 40 percent of a patient’s health, while just 20 percent were tied to care access and quality of care, the American Hospital Association (AHA) recently reported.

Despite the impact SDOH has on a patient’s outcomes and costs, many providers are not equipped to address housing, economic stability, education, food security, and other social determinants.

Providers in a recent Leavitt Partners survey cited insufficient appointment time and lack of compensation as top barriers to addressing SDOHs. Fee-for-service payments do not reimburse providers for extending care beyond the practice’s or hospital’s walls and even some alternative payment models have yet to branch out into integrating medical, social, and behavioral services.

This approach requires a collaborative approach and unique leadership skill to develop, maintain and develop resources, both financial and human to attain.

It is a brave new world with enormous opportunities as organizations and providers realize an ability to influence SDOH as never before.

In the past providers have recognized this aspect of patient care, with little resources to affect the major SOH affecting patient care as well as prevention

Patients can also contribute to this concept by communicating these needs and fully encompass a patient-centered health system.


Readers who want a deeper look









https://tinyurl.com/uomf8jo

Factors Affecting Clinician Well-Being and Resilience – Conceptual Model – Clinician Well-Being Knowledge Hub

What is  Physician Burnout?

It is the beginning of a new year and a new decade. Most of this month's work will address physician wellness, which very much affects every patient. Patients have become aware of physician burnout. Burnout is characterized by three components: (1) emotional exhaustion or loss of passion for one’s work, (2) depersonalization or treating patients as objects, and (3) the sense that your work is no longer meaningful;  caused by the rapid influx of technology, increased patient volume, a new payment method based upon the value, rather than the volume of patient visits. Physicians and patients usually have their forums and spaces. It used to be the 'doctor's lounge' or the doctor's dining room. This has become much less true in recent years. While the administrative suites have grown larger, the spaces set aside for physicians has decreased and perhaps has contributed to a loss of self-esteem.

Many physicians now blog in public blog spaces, have their facebook pages and Instagram page While web pages are static social media offers an almost synchronous platform for doctors and patients to communicate. Add to that secure messaging and telemedicine, the internet provides an almost spider web for communications, physician-patient-patient-physician.

This conceptual model was developed by the National Academy of Medicine Action Collaborative on Clinician Well-Being.

What is Clinician Burnout?

This conceptual model depicts the factors associated with clinician well-being and resilience; applies these factors across all health care professions, specialties, settings, and career stages; and emphasizes the link between clinician well-being and outcomes for clinicians, patients, and the health system. The model should be used to understand well-being, rather than as a diagnostic or assessment tool. The model will be revised as the field develops and more information becomes available.

The external and individual factors of the conceptual model are hyperlinked to corresponding landing pages on the Knowledge Hub, allowing users to navigate seamlessly between the two resources. By viewing the Conceptual Model on your computer, you will find that each factor is linked to a landing page within the Knowledge Hub. Each landing page provides additional information and resources.

 The body of medical literature on burnout has demonstrated significant professional repercussions including decreased patient satisfaction, increased medical errors and litigation, and the personal consequences of substance abuse and depression [5–7]. One proposed solution to physician burnout is to address physician wellness [8, 9]

Numerous study groups have evaluated this subject and published their results and recommendations.

Transforming Clinical Documentation in EHRs for 2020: Recommendations from the University of Minnesota's Big Data Conference Working Group

The Royal Society of Medicine Open Section’s Medical Humanities Conference: Physician Resilience and Compassionate Practice

Physicians have in the past been at the top of the hierarchy of responsibility.  Leadership is a lonely place, and the inability to share responsibility and authority comes with a price. Today's brand of medicine is a team approach. This is demonstrated by a number of reports

Team Structure and Culture Are Associated with Lower Burnout in Primary Care

Factors Affecting Clinician Well-Being and Resilience – Conceptual Model – Clinician Well-Being Knowledge Hub: Factors Affecting Clinician Well-Being and Resilience – Conceptual Model

******HAPPY NEW YEAR 2020*****

Why six trends are pointing to a revolution in healthcare | Health Data Management

Healthcare is in the midst of a dramatic shift, as new players surge into the business of health.

The latest step in this evolution came Friday, with reports that Walmart is in discussions to partner with—or perhaps even acquire—Humana, one of the nation’s largest insurers.

If these reports come to fruition, it would represent the latest in a series of new companies showing renewed interest in consumer health—a divergence in the way that the nation has treated health in years past. The move away from sick care to health preservation is built on six trends—and of those, a unifying theme is that the technological acumen and infrastructure is in place to support this shift.

Consumerism

It’s taken a while, but consumer-patients have taken more responsibility for their own care. For a generation now, an increasing number of people no longer rely solely on what they’re told by their medical providers. They’re researching medical conditions on the Internet and wanting to know more about their treatment options. Consumers also are demanding control over their medical information and seeking to add their own patient-reported data to it.

This involvement is no accident, nor by the thoughtfulness of patients.  Anyone seeing a physician or admitted to a hospital sees how busy providers are, and much of the medical information and is automated.  Machines have great memories but do not exercise executive life or death decisions.

This evolution came about when someone asked: "why can't medicine work like an airline or a bank" Everyone said, "yeah" great idea, then along came the gurus of information systems. Then they did it. No one asked are the cultures the same?   Information technology came to medicine late in the game. Medicine is one of the last bastions of the pen and paper. Our cognitive processes of writing by hand and typing on a keyboard are very different. This may very well be the major factor in physician burnout.  The conversion takes time and energy to discard a time-worn process into a new paradigm.

Patients are rightfully concerned about the accuracy of their records,  even if the provider knows who they are. They correctly ask questions, do research before the visit and are careful to remind their caregivers who they are and what their conditions are.  It is even worse for the nurses and paramedical assistants who screen the patient robotically recording their findings.


Business migration

New players are casting an eye at healthcare as both opportunity and business imperative. The recognition of the rise of consumerism is reflected in the companies now looking for a place to play within the health industry—Amazon, Apple, CVS, Walmart, and Walgreens, to name a few. These companies have deep experience and data systems necessary for dealing with the customer as a consumer. Similarly, traditional health insurers see their long-time business approaches changing. For decades, insurers have primarily served as care purchasers—the entities through which patients’ bills were filtered, often in a contentious duel with care providers. Increasingly, health insurers see their roles changing, because they are no longer the only entities taking on the actuarial risk of care. To a greater extent, consumers and providers are taking on those roles. Insurers increasingly want to see their roles morph, providing data and services that improve patient care and optimize consumer health. Hence, they are seeking partners that enable them to take on a broader role in health.

Price frustration

Initiatives intended to slow the rise of healthcare prices over the last three decades have ultimately failed to slow the rise in healthcare expenses. That’s why the U.S. spends more than $3 trillion dollars on healthcare annually, and why it’s no longer acceptable for solutions to aim to only slow the rate of growth. Healthcare currently consumes 18 percent of the gross domestic product, and the trendline is not good, especially as more Baby Boomers retire and are likely to see their medical needs—and costs—increase.







Why six trends are pointing to a revolution in healthcare | Health Data Management: The Walmart-Humana combination is the latest of a series of moves that point to an abrupt change in the industry.

JAMA Articles of the Decade-Happy New Year

We can look back and see the most important medical issues from 2012-2019 from the Journal of the American Medical Association.  This is an in-depth compilation of the most significant published articles from the peer-reviewed JAMAs

The articles have been selected by editors as the most important published by JAMA between 2010 and 2019. Click below to read them for free.

The Top Articles from 2010-2019

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Mervyn Singer, MD, FRCP; Clifford S. Deutschman, MD, MS; Christopher Warren Seymour, MD, MSc; et alManu

Abstract
Importance  Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.

Objective  To evaluate and, as needed, update definitions for sepsis and septic shock.

Process  A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment).

Key Findings From Evidence Synthesis  Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant.

Recommendations  Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.

Conclusions and Relevance  These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)

Paul A. James, MD; Suzanne Oparil, MD; Barry L. Carter, PharmD; et al

Audio Interview: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults

Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial

Paulina Salminen, MD, PhD; Hannu Paajanen, MD, PhD; Tero Rautio, MD, PhD; et al

Clinical Review Audio: Treating Appendicitis Without Surgery – 5-Year Follow-up From a Randomized Clinical Trial of Antibiotic Treatment

Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial

Jeff D. Williamson, MD, MHS; Mark A. Supiano, MD; William B. Applegate, MD, MPH; et al for the SPRINT Research Group

Video Interview: Intensive Blood Pressure Control in Adults Aged 75 Years or Older

Development and Validation of a Deep Learning Algorithm for Detection of Diabetic Retinopathy in Retinal Fundus Photographs

Varun Gulshan, PhD; Lily Peng, MD, PhD; Marc Coram, PhD; et al

Machine Learning Website

United States Health Care Reform: Progress to Date and Next Steps

Barack Obama, JD

Health Care Spending in the United States and Other High-Income Countries

Irene Papanicolas, PhD; Liana R. Woskie, MSc; Ashish K. Jha, MD, MPH

Video Interview: Health Care Spending in the United States and Other High-Income Countries

The Association Between Income and Life Expectancy in the United States, 2001-2014

Raj Chetty, PhD; Michael Stepner, BA; Sarah Abraham, BA; et al

JAMA Health Disparities Website

Audio Interview: Association Between Income and Life Expectancy in the United States

Video Interview: Association Between Income and Life Expectancy in the United States



Eliminating Waste in US Health Care

Donald M. Berwick, MD, MPP; Andrew D. Hackbarth, MPhil

Abstract
The need is urgent to bring US health care costs into a sustainable range for both public and private payers. Commonly, programs to contain costs use cuts, such as reductions in payment levels, benefit structures, and eligibility. A less harmful strategy would reduce waste, not value-added care. The opportunity is immense. In just 6 categories of waste—overtreatment, failures of care coordination, failures in the execution of care processes, administrative complexity, pricing failures, and fraud and abuse—the sum of the lowest available estimates exceeds 20% of total health care expenditures. The actual total may be far greater. The savings potentially achievable from systematic, comprehensive, and cooperative pursuit of even a fractional reduction in waste are far higher than from more direct and blunter cuts in care and coverage. The potential economic dislocations, however, are severe and require mitigation through careful transition strategies.

No matter how polarized politics in the United States have become, nearly everyone agrees that health care costs are unsustainable. At almost 18% of the gross domestic product (GDP) in 2011, headed for 20% by 2020,1,2 the nation's increasing health care expenditures reduce the resources available for other worthy government programs, erode wages, and undermine the competitiveness of US industry. Although Medicare and Medicaid are often in the limelight, the health care cost problem affects the private sector just as much as the public sector. Both need serious relief.

Obtaining savings directly—by simply lowering payments or paying for fewer services—seems the most obvious remedy. Programs designed to make cuts of this kind appear across the policy spectrum, from many, carefully sequenced provisions of the Patient Protection and Affordable Care Act (ACA), favored by the Obama Administration, to draconian proposed shifts of Medicare costs to beneficiaries and reductions in payments to physicians and hospitals, favored by several Republican congressional proponents.

The ACA, for example, gradually phases in well-warranted decreases in payments to Medicare Advantage plans. Some in Congress have proposed caps on federal Medicare payments (with beneficiaries picking up the difference). Many states, reeling from unprecedented budget deficits, are reducing Medicaid benefits and payments.

The cost reductions in the ACA are necessary and prudent, but if other initiatives to cut spending are taken too far or too fast, they become risky. Vulnerable Medicaid beneficiaries and seniors covered by Medicare with marginal incomes may find important care services out of reach, either because they cannot afford the new cost-sharing, because clinicians and hospitals have withdrawn from local markets, or both.


Silencing the Science on Gun Research

Arthur L. Kellermann, MD, MPH; Frederick P. Rivara, MD, MPH

2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults

Abstract

Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes.

There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes.

Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.

Hypertension remains one of the most important preventable contributors to disease and death. Abundant evidence from randomized controlled trials (RCTs) has shown benefit of antihypertensive drug treatment in reducing important health outcomes in persons with hypertension.^1-3 Clinical guidelines are at the intersection between research evidence and clinical actions that can improve patient outcomes. The Institute of Medicine Report Clinical Practice Guidelines We Can Trust outlined a pathway to guideline development and is the approach that this panel aspired to in the creation of this report.⁴

Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis
The APPAC Randomized Clinical  


Abstract
Importance  An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis.

Objective  To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT).

Design, Setting, and Participants  The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period.

Interventions  Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy.

Main Outcomes and Measures  The primary endpoint for the surgical intervention was the successful completion of an appendectomy. The primary endpoint for antibiotic-treated patients was discharged from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period.

Results  There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of −27.0% (95% CI, −31.6% to ∞) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate the noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment.

Conclusions and Relevance  Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications.

Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years
A Randomized Clinical Trial

Abstract
Importance  The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain.

Objective  To evaluate the effects of intensive (<120 75="" aged="" but="" compared="" diabetes.="" hg="" hypertension="" in="" mm="" older="" or="" p="" persons="" sbp="" standard="" targets="" with="" without="" years="">
Design, Setting, and Participants  A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015.

Interventions  Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319).

Main Outcomes and Measures  The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome.

Results  Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]).

Conclusions and Relevance  Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.

Development and Validation of a Deep Learning Algorithm for Detection of Diabetic Retinopathy in Retinal Fundus Photographs
Varun Gulshan, PhD1; Lily Peng, MD, PhD1; Marc Coram, PhD1; et al

Finding  In 2 validation sets of 9963 images and 1748 images, at the operating point selected for high specificity, the algorithm had 90.3% and 87.0% sensitivity and 98.1% and 98.5% specificity for detecting referable diabetic retinopathy, defined as moderate or worse diabetic retinopathy or referable macular edema by the majority decision of a panel of at least 7 US board-certified ophthalmologists. At the operating point selected for high sensitivity, the algorithm had 97.5% and 96.1% sensitivity and 93.4% and 93.9% specificity in the 2 validation sets.

Meaning  Deep learning algorithms had high sensitivity and specificity for detecting diabetic retinopathy and macular edema in retinal fundus photographs.

Abstract
Importance  Deep learning is a family of computational methods that allow an algorithm to program itself by learning from a large set of examples that demonstrate the desired behavior, removing the need to specify rules explicitly. The application of these methods to medical imaging requires further assessment and validation.

Objective  To apply deep learning to create an algorithm for automated detection of diabetic retinopathy and diabetic macular edema in retinal fundus photographs.

Design and Setting  A specific type of neural network optimized for image classification called a deep convolutional neural network was trained using a retrospective development data set of 128 175 retinal images, which were graded 3 to 7 times for diabetic retinopathy, diabetic macular edema, and image gradability by a panel of 54 US licensed ophthalmologists and ophthalmology senior residents between May and December 2015. The resultant algorithm was validated in January and February 2016 using 2 separate data sets, both graded by at least 7 US board-certified ophthalmologists with high intragrader consistency.

Exposure  Deep learning–trained algorithm.

Main Outcomes and Measures  The sensitivity and specificity of the algorithm for detecting referable diabetic retinopathy (RDR), defined as moderate and worse diabetic retinopathy, referable diabetic macular edema, or both, were generated based on the reference standard of the majority decision of the ophthalmologist panel. The algorithm was evaluated at 2 operating points selected from the development set, one selected for high specificity and another for high sensitivity.

Results  The EyePACS-1 data set consisted of 9963 images from 4997 patients (mean age, 54.4 years; 62.2% women; prevalence of RDR, 683/8878 fully gradable images [7.8%]); the Messidor-2 data set had 1748 images from 874 patients (mean age, 57.6 years; 42.6% women; prevalence of RDR, 254/1745 fully gradable images [14.6%]). For detecting RDR, the algorithm had an area under the receiver operating curve of 0.991 (95% CI, 0.988-0.993) for EyePACS-1 and 0.990 (95% CI, 0.986-0.995) for Messidor-2. Using the first operating cut point with high specificity, for EyePACS-1, the sensitivity was 90.3% (95% CI, 87.5%-92.7%) and the specificity was 98.1% (95% CI, 97.8%-98.5%). For Messidor-2, the sensitivity was 87.0% (95% CI, 81.1%-91.0%) and the specificity was 98.5% (95% CI, 97.7%-99.1%). Using a second operating point with high sensitivity in the development set, for EyePACS-1 the sensitivity was 97.5% and specificity was 93.4% and for Messidor-2 the sensitivity was 96.1% and specificity was 93.9%.

Conclusions and Relevance  In this evaluation of retinal fundus photographs from adults with diabetes, an algorithm based on deep machine learning had high sensitivity and specificity for detecting referable diabetic retinopathy. Further research is necessary to determine the feasibility of applying this algorithm in the clinical setting and to determine whether the use of the algorithm could lead to improved care and outcomes compared with the current ophthalmologic assessment.

United States Health Care Reform
Progress to Date and Next Steps
Barack Obama, JD1

Abstract
Importance  The Affordable Care Act is the most important health care legislation enacted in the United States since the creation of Medicare and Medicaid in 1965. The law implemented comprehensive reforms designed to improve the accessibility, affordability, and quality of health care.

Objectives  To review the factors influencing the decision to pursue health reform, summarize evidence on the effects of the law to date, recommend actions that could improve the health care system, and identify general lessons for public policy from the Affordable Care Act.

Evidence  Analysis of publicly available data, data obtained from government agencies, and published research findings. The period examined extends from 1963 to early 2016.

Findings  The Affordable Care Act has made significant progress toward solving long-standing challenges facing the US health care system related to access, affordability, and quality of care. Since the Affordable Care Act became law, the uninsured rate has declined by 43%, from 16.0% in 2010 to 9.1% in 2015, primarily because of the law’s reforms. Research has documented accompanying improvements in access to care (for example, an estimated reduction in the share of nonelderly adults unable to afford care of 5.5 percentage points), financial security (for example, an estimated reduction in debts sent to collection of $600-$1000 per person gaining Medicaid coverage), and health (for example, an estimated reduction in the share of nonelderly adults reporting fair or poor health of 3.4 percentage points). The law has also begun the process of transforming health care payment systems, with an estimated 30% of traditional Medicare payments now flowing through alternative payment models like bundled payments or accountable care organizations. These and related reforms have contributed to a sustained period of slow growth in per-enrollee health care spending and improvements in health care quality. Despite this progress, major opportunities to improve the health care system remain.

Conclusions and Relevance  Policymakers should build on progress made by the Affordable Care Act by continuing to implement the Health Insurance Marketplaces and delivery system reform, increasing federal financial assistance for Marketplace enrollees, introducing a public plan option in areas lacking individual market competition, and taking actions to reduce prescription drug costs. Although partisanship and special interest opposition remain, experience with the Affordable Care Act demonstrates that positive change is achievable on some of the nation’s most complex challenges.

Health Care Spending in the United States and Other High-Income Countries
Irene Papanicolas, PhD; Liana R. Woskie, MSc; Ashish K. Jha, MD, MPH
JAMA Articles of the Decade

Abstract
Importance of Health care spending in the United States is a major concern and is higher than in other high-income countries, but there is little evidence that efforts to reform US health care delivery have had a meaningful influence on controlling health care spending and costs.

Objective  To compare potential drivers of spending, such as structural capacity and utilization, in the United States with those of 10 of the highest-income countries (United Kingdom, Canada, Germany, Australia, Japan, Sweden, France, the Netherlands, Switzerland, and Denmark) to gain insight into what the United States can learn from these nations.

Evidence  Analysis of data primarily from 2013-2016 from key international organizations including the Organisation for Economic Co-operation and Development (OECD), comparing underlying differences in structural features, types of health care and social spending, and performance between the United States and 10 high-income countries. When data were not available for a given country or more accurate country-level estimates were available from sources other than the OECD, country-specific data sources were used.

Findings  In 2016, the US spent 17.8% of its gross domestic product on health care, and spending in the other countries ranged from 9.6% (Australia) to 12.4% (Switzerland). The proportion of the population with health insurance was 90% in the US, lower than the other countries (range, 99%-100%), and the US had the highest proportion of private health insurance (55.3%). For some determinants of health such as smoking, the US ranked second-lowest of the countries (11.4% of the US population ≥15 years smokes daily; mean of all 11 countries, 16.6%), but the US had the highest percentage of adults who were overweight or obese at 70.1% (range for other countries, 23.8%-63.4%; mean of all 11 countries, 55.6%). Life expectancy in the US was the lowest of the 11 countries at 78.8 years (range for other countries, 80.7-83.9 years; mean of all 11 countries, 81.7 years), and infant mortality was the highest (5.8 deaths per 1000 live births in the US; 3.6 per 1000 for all 11 countries). The US did not differ substantially from the other countries in the physician workforce (2.6 physicians per 1000; 43% primary care physicians), or nursing workforce (11.1 nurses per 1000). The US had comparable numbers of hospital beds (2.8 per 1000) but higher utilization of magnetic resonance imaging (118 per 1000) and computed tomography (245 per 1000) vs other countries. The US had similar rates of utilization (US discharges per 100 000 were 192 for acute myocardial infarction, 365 for pneumonia, 230 for chronic obstructive pulmonary disease; procedures per 100 000 were 204 for hip replacement, 226 for knee replacement, and 79 for coronary artery bypass graft surgery). Administrative costs of care (activities relating to planning, regulating, and managing health systems and services) accounted for 8% in the US vs a range of 1% to 3% in the other countries. For pharmaceutical costs, spending per capita was $1443 in the US vs a range of $466 to $939 in other countries. Salaries of physicians and nurses were higher in the US; for example, generalist physicians' salaries were $218 173 in the US compared with a range of $86 607 to $154 126 in the other countries.

Conclusions and Relevance  The United States spent approximately twice as much as other high-income countries on medical care, yet utilization rates in the United States were largely similar to those in other nations. Prices of labor and goods, including pharmaceuticals, and administrative costs appeared to be the major drivers of the difference in overall cost between the United States and other high-income countries. As patients, physicians, policymakers, and legislators actively debate the future of the US health system, data such as these are needed to inform policy decisions.

The Association Between Income and Life Expectancy in the United States, 2001-2014

Raj Chetty, PhD; Michael Stepner, BA; Sarah Abraham, BA; et al

Abstract

Importance  The relationship between income and life expectancy is well established but remains poorly understood.

Objectives  To measure the level, time trend, and geographic variability in the association between income and life expectancy and to identify factors related to small area variation.

Design and Setting  Income data for the US population were obtained from 1.4 billion deidentified tax records between 1999 and 2014. Mortality data were obtained from Social Security Administration death records. These data were used to estimate race- and ethnicity-adjusted life expectancy at 40 years of age by household income percentile, sex, and geographic area, and to evaluate factors associated with differences in life expectancy.

Exposure  Pretax household earnings as a measure of income.

Main Outcomes and Measures  Relationship between income and life expectancy; trends in life expectancy by income group; geographic variation in life expectancy levels and trends by income group; and factors associated with differences in life expectancy across areas.

Results  The sample consisted of 1 408 287 218 person-year observations for individuals aged 40 to 76 years (mean age, 53.0 years; median household earnings among working individuals, $61 175 per year). There were 4 114 380 deaths among men (mortality rate, 596.3 per 100 000) and 2 694 808 deaths among women (mortality rate, 375.1 per 100 000). The analysis yielded 4 results. First, higher income was associated with greater longevity throughout the income distribution. The gap in life expectancy between the richest 1% and poorest 1% of individuals was 14.6 years (95% CI, 14.4 to 14.8 years) for men and 10.1 years (95% CI, 9.9 to 10.3 years) for women. Second, inequality in life expectancy increased over time. Between 2001 and 2014, life expectancy increased by 2.34 years for men and 2.91 years for women in the top 5% of the income distribution, but by only 0.32 years for men and 0.04 years for women in the bottom 5% (P < .001 for the differences for both sexes). Third, life expectancy for low-income individuals varied substantially across local areas. In the bottom income quartile, life expectancy differed by approximately 4.5 years between areas with the highest and lowest longevity. Changes in life expectancy between 2001 and 2014 ranged from gains of more than 4 years to losses of more than 2 years across areas. Fourth, geographic differences in life expectancy for individuals in the lowest income quartile were significantly correlated with health behaviors such as smoking (r = −0.69, P < .001), but were not significantly correlated with access to medical care, physical environmental factors, income inequality, or labor market conditions. Life expectancy for low-income individuals was positively correlated with the local area fraction of immigrants (r = 0.72, P < .001), fraction of college graduates (r = 0.42, P < .001), and government expenditures (r = 0.57, P < .001).

Conclusions and Relevance  In the United States between 2001 and 2014, higher income was associated with greater longevity, and differences in life expectancy across income groups increased over time. However, the association between life expectancy and income varied substantially across areas; differences in longevity across income groups decreased in some areas and increased in others. The differences in life expectancy were correlated with health behaviors and local area characteristics.

Silencing the Science on Gun Research . Arthur L. Kellermann, MD, MPH; Frederick P. Rivara, MD, MPH

On December 14, a 20-year-old Connecticut man shot and killed his mother in the home they shared. Then, armed with 3 of his mother's guns, he shot his way into a nearby school, where he killed 6 additional adults and 20 first-grade children. Most of those who died were shot repeatedly at close range. Soon thereafter, the killer shot himself. This ended the carnage but greatly diminished the prospects that anyone will ever know why he chose to commit such horrible acts.

In body count, this incident in Newtown ranks second among US mass shootings. It follows recent mass shootings in a shopping mall in Oregon, a movie theater in Colorado, a Sikh temple in Wisconsin, and a business in Minnesota. These join a growing list of mass killings in such varied places as a high school, a college campus, a congressional constituent meeting, a day trader's offices, and a military base. But because this time the killer's target was an elementary school, and many of his victims were young children, this incident shook a nation some thought was inured to gun violence.

As shock and grief give way to anger, the urge to act is powerful. But beyond helping the survivors deal with their grief and consequences of this horror, what can the medical and public health community do? What actions can the nation take to prevent more such acts from happening, or at least limit their severity? More broadly, what can be done to reduce the number of US residents who die each year from firearms, currently more than 31 000 annually?1

The answers are undoubtedly complex and at this point, only partly known. For gun violence, particularly mass killings such as that in Newtown, to occur, intent and means must converge at a particular time and place. Decades of research have been devoted to understanding the factors that lead some people to commit violence against themselves or others. Substantially less has been done to understand how easy access to firearms mitigates or amplifies both the likelihood and consequences of these acts.

For example, background checks have an effect on inappropriate procurement of guns from licensed dealers, but private gun sales require no background check. Laws mandating a minimum age for gun ownership reduce gun fatalities, but firearms still pass easily from legal owners to juveniles and other legally proscribed individuals, such as felons or persons with mental illness. Because ready access to guns in the home increases, rather than reduces, a family's risk of homicide in the home, safe storage of guns might save lives.2 Nevertheless, many gun owners, including gun-owning parents, still keep at least one firearm loaded and readily available for self-defense.3

The nation might be in a better position to act if medical and public health researchers had continued to study these issues as diligently as some of us did between 1985 and 1997. But in 1996, pro-gun members of Congress mounted an all-out effort to eliminate the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention (CDC). Although they failed to defund the center, the House of Representatives removed $2.6 million from the CDC's budget—precisely the amount the agency had spent on firearm injury research the previous year. Funding was restored in joint conference committee, but the money was earmarked for traumatic brain injury. The effect was sharply reduced support for firearm injury research.

To ensure that the CDC and its grantees got the message, the following language was added to the final appropriation: “none of the funds made available for injury prevention and control at the Centers for Disease Control and Prevention may be used to advocate or promote gun control.”4

Precisely what was or was not permitted under the clause was unclear. But no federal employee was willing to risk his or her career or the agency's funding to find out. Extramural support for firearm injury prevention research quickly dried up. Even today, 17 years after this legislative action, the CDC's website lacks specific links to information about preventing firearm-related violence.

When other agencies funded high-quality research, similar action was taken. In 2009, Branas et al5 published the results of a case-control study that examined whether carrying a gun increases or decreases the risk of firearm assault. In contrast to earlier research, this particular study was funded by the National Institute on Alcohol Abuse and Alcoholism. Two years later, Congress extended the restrictive language it had previously applied to the CDC to all Department of Health and Human Services agencies, including the National Institutes of Health.6

These are not the only efforts to keep important health information from the public and patients. For example, in 1997, Cummings et al7 used state-level data from Washington to study the association between purchase of a handgun and the subsequent risk of homicide or suicide. Similar studies could not be conducted today because Washington State's firearm registration files are no longer accessible.8

In 2011, Florida's legislature passed and Governor Scott signed HB 155, which subjects the state's health care practitioners to possible sanctions, including loss of license, if they discuss or record information about firearm safety that a medical board later determines was not “relevant” or was “unnecessarily harassing.” A US district judge has since issued a preliminary injunction to block enforcement of this law, but the matter is still in litigation. Similar bills have been proposed in 7 other states.

The US military is grappling with an increase in suicides within its ranks. Earlier this month, an article by 2 retired generals—a former chief and a vice chief of staff of the US Army— asked Congress to lift a little-noticed provision in the 2011 National Defense Authorization Act that prevents military commanders and noncommissioned officers from being able to talk to service members about their private weapons, even in cases in which a leader believes that a service member may be suicidal.9

Health researchers are ethically bound to conduct, analyze, and report studies as objectively as possible and communicate the findings in a transparent manner. Policy makers, health care practitioners, and the public have the final decision regarding whether they will accept, much less act on, those data. Criticizing research is fair game; suppressing research by targeting its sources of funding is not.

Efforts to place legal restrictions on what physicians and other health care practitioners can and cannot say to their patients crosses an even more important line. Yet this is precisely what Florida and some other states are seeking to do. Physicians may disagree on many issues, including the pros and cons of gun control, but are united in opposing government efforts to undermine the sanctity of the patient-physician relationship, as defined by the Hippocratic oath. While it is reasonable to acknowledge and accept the Supreme Court's recent decision regarding the meaning of the Second Amendment, it is just as important to uphold physicians' First Amendment rights.

Injury prevention research can have real and lasting effects. Over the last 20 years, the number of Americans dying in motor vehicle crashes has decreased by 31%.1 Deaths from fires and drowning have been reduced even more, by 38% and 52%, respectively.1 This progress was achieved without banning automobiles, swimming pools, or matches. Instead, it came from translating research findings into effective interventions.

Given the chance, could researchers achieve similar progress with firearm violence? It will not be possible to find out unless Congress rescinds its moratorium on firearm injury prevention research. Since Congress took this action in 1997, at least 427 000 people have died of gunshot wounds in the United States, including more than 165 000 who were victims of homicide.1 To put these numbers in context, during the same time period, 4586 Americans lost their lives in combat in Iraq and Afghanistan.10

The United States has long relied on public health science to improve the safety, health, and lives of its citizens. Perhaps the same straightforward, problem-solving approach that worked well in other circumstances can help the nation meet the challenge of firearm violence. Otherwise, the heartache that the nation and perhaps the world is feeling over the senseless gun violence in Newtown will likely be repeated, again and again.

Bibliography

  

THE UNFORTUNATE RISE OF STEM CELL CLINICS

Stem Cell Therapy is not ready for widespread unregulated use.

MSCs and other stem cells offer remarkable potential but our understanding of their science and medical applications is not ready for unregulated, widespread use. The complexity of tissue repair and cell replacement makes it clear that the proliferation of questionable “stem cell clinics” and off-shore medical tourism offices promoting their autologous “stem cell treatments” of unknown and unproven efficacy will not solve patient maladies in a meaningful way. The divergence between reputable clinical trials and the premature marketing of stem cell products to the public has broadened the gap and led to confusion in the press as highlighted by Galipeau et al.15 There are over 700 clinics offering direct-to-consumer marketing of “stem cell” treatments.16 We cannot support or recommend any treatment utilizing MSCs that does not use characterized cell product, maintain accurate records, measure intermediate parameters, predetermined surrogate endpoints and track and report final patient outcome(s). These steps are common practice in FDA registered trials, but too demanding for under- or unregulated clinics. A recent study (see Murray et al.16 reference for details) has offered a consensus report on the parameters needed to improve cell therapy outcomes for both patients and practitioners using the acronym DOSES: D—Donor, O—Origin tissue, S—Separation Method, E—Exhibited Characteristics, S—Site of Delivery.

Stem Cell Clinics may reference their stem cell lineage as bone marrow stem cells, amniotic membrane stem cells, fat cell and mesenchymal in origin.

Adult/Tissue Stem Cells
Adult stem cells, or “tissue stem cells,” can come from different parts of the adult body. They are specific to a certain kind of tissue in the body: for instance, liver stem cells can regenerate liver tissue, and muscle stem cells can regenerate muscle fibers. But adult stem cells are limited to only becoming more of their specialized tissue—liver stem cells cannot make new muscle fibers, nor can muscle stem cells make new liver tissue.

Cells

The thousands of different cell types that make up our bodies all came from one single “master builder” cell, called a pluripotent stem cell.

Pluripotent stem cells can be thought of as “blank slates,” because of their ability to build any cell type in the body—skin cells, brain cells, muscle cells, etc. Unlike tissue stem cells, pluripotent stem cells are not limited to only becoming more of a certain tissue.
Pluripotent stem cells primarily consist of embryonic stem cells, but the term now also encompasses another type of cells, called “induced pluripotent stem cells.” More on that later.

Induced Pluripotent Stem Cells/iPSCs
Induced pluripotent stem (iPS) cells are pluripotent cells that are derived from adult tissue using new scientific technology. They share characteristics with embryonic stem cells in that they can become any cell type in the body.

Reprogramming stem cells to create iPSCs involves some genetic manipulation, and this may cause some differences that are not present in cells that are already embryonic in nature. It is essential to continue research using all cell types. Because the field of stem cell research is so new, it is critical to explore all avenues of stem cell research, from pluripotent to tissue stem cells.

Although research has been in progress for the past decade or more, we are just beginning to unravel how the embryonic ova differentiates with each cell division. Each division results in an exponential increase in the number of stem cells. With each division, the pluripotential of each cell decreases in an inverse manner. In other words, they will not have the same potential to make certain kinds of tissue (brain, skin, bones, liver, and other organ systems.  At maturity and at birth some organs contain a reservoir of stem cells particular to that tissue.  Organs with demand for higher cellular division to repopulate the organ such as skin, bone marrow.  Skin as an organ continuously requires replacement as the upper layers are shed.  The normal time of RBC senescent (age-related) death in adults is approximately 110 to 120 days through a process call erythropoiesis.

Blood Stem cells go on to differentiate as shown in the figure.(s)

Red blood cells are manufactured by a complex loop of protein regulation from the liver and kidneys. The rate is normally 2-3 million RBCs /second when the system is stable, with an equal amount of senescent RBCs being destroyed by eryptosis (scroll down)

This process is balanced by RBC senescence or eryptosis.  

Another stem cell line follows a journey much like the progenitor hemocytoblast. The basal layers of skin contain stem cells that begin the process. There are many skin products that claim to stimulate the process using DNA like analog molecules.

The production of a focused stem cell requires an arduous process of trial and error in the lab. Once this is accomplished a Clinical trial will be submitted to the FDA for approval to market the drug. They determine the safety, efficacy and side effects or complication by using the drug in humans.

Early pre-trial studies are done in mice when possible.

Biblio:

15 Galipeau, J., Weiss, D. J. & Dominici, M. Response to Nature commentary “Clear up this stem-cell mess”. Cytotherapy 21, 1–2 (2019).
16 Murray, I. R. et al. International expert consensus on a cell therapy communication tool: DOSES. J. Bone Jt. Surg.
* Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement