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Saturday, February 22, 2020

Preventive healthcare

From Wikipedia, the free encyclopedia
Immunization against diseases is a key preventive healthcare measure.

Preventive healthcare (alternatively preventative healthcare or prophylaxis) consists of measures taken for disease prevention. Disease and disability are affected by environmental factors, genetic predisposition, disease agents, and lifestyle choices and are dynamic processes which begin before individuals realize they are affected. Disease prevention relies on anticipatory actions that can be categorized as primal, primary, secondary, and tertiary prevention.

Each year, millions of people die of preventable deaths. A 2004 study showed that about half of all deaths in the United States in 2000 were due to preventable behaviors and exposures. Leading causes included cardiovascular disease, chronic respiratory disease, unintentional injuries, diabetes, and certain infectious diseases. This same study estimates that 400,000 people die each year in the United States due to poor diet and a sedentary lifestyle. According to estimates made by the World Health Organization (WHO), about 55 million people died worldwide in 2011, two thirds of this group from non-communicable diseases, including cancer, diabetes, and chronic cardiovascular and lung diseases. This is an increase from the year 2000, during which 60% of deaths were attributed to these diseases. Preventive healthcare is especially important given the worldwide rise in prevalence of chronic diseases and deaths from these diseases.

There are many methods for prevention of disease. One of them is prevention of teenage smoking through information giving. It is recommended that adults and children aim to visit their doctor for regular check-ups, even if they feel healthy, to perform disease screening, identify risk factors for disease, discuss tips for a healthy and balanced lifestyle, stay up to date with immunizations and boosters, and maintain a good relationship with a healthcare provider. Some common disease screenings include checking for hypertension (high blood pressure), hyperglycemia (high blood sugar, a risk factor for diabetes mellitus), hypercholesterolemia (high blood cholesterol), screening for colon cancer, depression, HIV and other common types of sexually transmitted disease such as chlamydia, syphilis, and gonorrhea, mammography (to screen for breast cancer), colorectal cancer screening, a Pap test (to check for cervical cancer), and screening for osteoporosis. Genetic testing can also be performed to screen for mutations that cause genetic disorders or predisposition to certain diseases such as breast or ovarian cancer. However, these measures are not affordable for every individual and the cost effectiveness of preventive healthcare is still a topic of debate.

Levels of prevention

Preventive healthcare strategies are described as taking place at the primal, primary, secondary, and tertiary prevention levels. Although advocated as preventive medicine in the early twentieth century by Sara Josephine Baker, in the 1940s, Hugh R. Leavell and E. Gurney Clark coined the term primary prevention. They worked at the Harvard and Columbia University Schools of Public Health, respectively, and later expanded the levels to include secondary and tertiary prevention. Goldston (1987) notes that these levels might be better described as "prevention, treatment, and rehabilitation", although the terms primary, secondary, and tertiary prevention are still in use today. The concept of primal prevention has been created much more recently, in relation to the new developments in molecular biology over the last fifty years, more particularly in epigenetics, which point to the paramount importance of environmental conditions - both physical and affective - on the organism during its fetal and newborn life (or so-called primal period of life).

Level Definition
Primal and primordial prevention Any measure aimed at helping future parents provide their upcoming child with adequate attention, as well as secure physical and affective environments from conception to first birthday. Primordial prevention refers to measures designed to avoid the development of risk factors in the first place, early in life.
Primary prevention Methods to avoid occurrence of disease either through eliminating disease agents or increasing resistance to disease. Examples include immunization against disease, maintaining a healthy diet and exercise regimen, and avoiding smoking.
Secondary prevention Methods to detect and address an existing disease prior to the appearance of symptoms. Examples include treatment of hypertension (a risk factor for many cardiovascular diseases), and cancer screenings.
Tertiary prevention Methods to reduce the harm of symptomatic disease, such as disability or death, through rehabilitation and treatment. Examples include surgical procedures that halt the spread or progression of disease.
Quaternary prevention Methods to mitigate or avoid results of unnecessary or excessive interventions in the health system

Primal and primordial prevention

Primal prevention has recently been propounded as a separate category of "health promotion". This health promotion par excellence is based on the 'new knowledge' in molecular biology, in particular on epigenetic knowledge, which points to how much affective - as well as physical - environment during fetal and newborn life may determine each and every aspect of adult health. This new way of promoting health consists mainly in providing future parents with pertinent, unbiased information on primal health and supporting them during their child's primal period of life (i.e., "from conception to first anniversary" according to definition by the Primal Health Research Centre, London). This includes adequate parental leave - ideally for both parents - with kin caregiving and financial help where needed. 

Another related concept is primordial prevention which refers to all measures designed to prevent the development of risk factors in the first place, early in life.

Primary prevention

Primary prevention consists of traditional "health promotion" and "specific protection." Health promotion activities are current, non-clinical life choices. For example, eating nutritious meals and exercising daily, that both prevent disease and create a sense of overall well-being. Preventing disease and creating overall well-being, prolongs our life expectancy. Health-promotional activities do not target a specific disease or condition but rather promote health and well-being on a very general level. On the other hand, specific protection targets a type or group of diseases and complements the goals of health promotion.

Food is very much the most basic tool in preventive health care. The 2011 National Health Interview Survey performed by the Centers for Disease Control was the first national survey to include questions about ability to pay for food. Difficulty with paying for food, medicine, or both is a problem facing 1 out of 3 Americans. If better food options were available through food banks, soup kitchens, and other resources for low-income people, obesity and the chronic conditions that come along with it would be better controlled. A "food desert" is an area with restricted access to healthy foods due to a lack of supermarkets within a reasonable distance. These are often low-income neighborhoods with the majority of residents lacking transportation. There have been several grassroots movements in the past 20 years to encourage urban gardening, such as the GreenThumb organization in New York City. Urban gardening uses vacant lots to grow food for a neighborhood and is cultivated by the local residents. Mobile fresh markets are another resource for residents in a "food desert", which are specially outfitted buses bringing affordable fresh fruits and vegetables to low-income neighborhoods. These programs often hold educational events as well such as cooking and nutrition guidance. Programs such as these are helping to provide healthy, affordable foods to people who need them. 

Scientific advancements in genetics have significantly contributed to the knowledge of hereditary diseases and have facilitated great progress in specific protective measures in individuals who are carriers of a disease gene or have an increased predisposition to a specific disease. Genetic testing has allowed physicians to make quicker and more accurate diagnoses and has allowed for tailored treatments or personalized medicine. Similarly, specific protective measures such as water purification, sewage treatment, and the development of personal hygienic routines (such as regular hand-washing) became mainstream upon the discovery of infectious disease agents such as bacteria. These discoveries have been instrumental in decreasing the rates of communicable diseases that are often spread in unsanitary conditions. Preventing sexually transmitted infections is another form of primary prevention.

Secondary prevention

Secondary prevention deals with latent diseases and attempts to prevent an asymptomatic disease from progressing to symptomatic disease. Certain diseases can be classified as primary or secondary. This depends on definitions of what constitutes a disease, though, in general, primary prevention addresses the root cause of a disease or injury whereas secondary prevention aims to detect and treat a disease early on. Secondary prevention consists of "early diagnosis and prompt treatment" to contain the disease and prevent its spread to other individuals, and "disability limitation" to prevent potential future complications and disabilities from the disease. For example, early diagnosis and prompt treatment for a syphilis patient would include a course of antibiotics to destroy the pathogen and screening and treatment of any infants born to syphilitic mothers. Disability limitation for syphilitic patients includes continued check-ups on the heart, cerebrospinal fluid, and central nervous system of patients to curb any damaging effects such as blindness or paralysis.

Tertiary prevention

Finally, tertiary prevention attempts to reduce the damage caused by symptomatic disease by focusing on mental, physical, and social rehabilitation. Unlike secondary prevention, which aims to prevent disability, the objective of tertiary prevention is to maximize the remaining capabilities and functions of an already disabled patient. Goals of tertiary prevention include: preventing pain and damage, halting progression and complications from disease, and restoring the health and functions of the individuals affected by disease. For syphilitic patients, rehabilitation includes measures to prevent complete disability from the disease, such as implementing work-place adjustments for the blind and paralyzed or providing counseling to restore normal daily functions to the greatest extent possible.

Leading causes of preventable death

United States

The leading cause of death in the United States was tobacco. However, poor diet and lack of exercise may soon surpass tobacco as a leading cause of death. These behaviors are modifiable and public health and prevention efforts could make a difference to reduce these deaths.

Leading causes of preventable deaths in the United States in the year 2000
Cause Deaths caused % of all deaths
Tobacco smoking 435,000 18.1
Poor diet and physical inactivity 400,000 16.6
Alcohol consumption 85,000 3.5
Infectious diseases 75,000 3.1
Toxicants 55,000 2.3
Traffic collisions 43,000 1.8
Firearm incidents 29,000 1.2
Sexually transmitted infections 20,000 0.8
Drug abuse 17,000 0.7

Worldwide

The leading causes of preventable death worldwide share similar trends to the United States. There are a few differences between the two, such as malnutrition, pollution, and unsafe sanitation, that reflect health disparities between the developing and developed world.

Leading causes of preventable death worldwide as of the year 2001
Cause Deaths caused (millions per year)
Hypertension 7.8
Smoking 5.0
High cholesterol 3.9
Malnutrition 3.8
Sexually transmitted infections 3.0
Poor diet 2.8
Overweight and obesity 2.5
Physical inactivity 2.0
Alcohol 1.9
Indoor air pollution from solid fuels 1.8
Unsafe water and poor sanitation 1.6

Child mortality

In 2010, 7.6 million children died before reaching the age of 5. While this is a decrease from 9.6 million in the year 2000, it is still far from the fourth Millennium Development Goal to decrease child mortality by two-thirds by the year 2015. Of these deaths, about 64% were due to infection (including diarrhea, pneumonia, and malaria). About 40% of these deaths occurred in neonates (children ages 1–28 days) due to pre-term birth complications. The highest number of child deaths occurred in Africa and Southeast Asia. In Africa, almost no progress has been made in reducing neonatal death since 1990. India, Nigeria, Democratic Republic of the Congo, Pakistan, and China contributed to almost 50% of global child deaths in 2010. Targeting efforts in these countries is essential to reducing the global child death rate.

Child mortality is caused by a variety of factors including poverty, environmental hazards, and lack of maternal education. The World Health Organization created a list of interventions in the following table that were judged economically and operationally "feasible," based on the healthcare resources and infrastructure in 42 nations that contribute to 90% of all infant and child deaths. The table indicates how many infant and child deaths could have been prevented in the year 2000, assuming universal healthcare coverage.

Leading preventive interventions that reduce deaths in children 0–5 years old worldwide
Intervention Percent of all child deaths preventable
Breastfeeding 13
Insecticide-treated materials 7
Complementary feeding 6
Zinc 4
Clean delivery 4
Hib vaccine 4
Water, sanitation, hygiene 3
Antenatal steroids 3
Newborn temperature management 2
Vitamin A 2
Tetanus toxoid 2
Nevirapine and replacement feeding 2
Antibiotics for premature rupture of membranes 1
Measles vaccine 1
Antimalarial intermittent preventive treatment in pregnancy <1 font="">

Preventive methods

Obesity

Obesity is a major risk factor for a wide variety of conditions including cardiovascular diseases, hypertension, certain cancers, and type 2 diabetes. In order to prevent obesity, it is recommended that individuals adhere to a consistent exercise regimen as well as a nutritious and balanced diet. A healthy individual should aim for acquiring 10% of their energy from proteins, 15-20% from fat, and over 50% from complex carbohydrates, while avoiding alcohol as well as foods high in fat, salt, and sugar. Sedentary adults should aim for at least half an hour of moderate-level daily physical activity and eventually increase to include at least 20 minutes of intense exercise, three times a week. Preventive health care offers many benefits to those that chose to participate in taking an active role in the culture. The medical system in our society is geared toward curing acute symptoms of disease after the fact that they have brought us into the emergency room. An ongoing epidemic within American culture is the prevalence of obesity. Eating healthier and routinely exercising plays a huge role in reducing an individual's risk for type 2 diabetes. About 23.6 million people in the United States have diabetes. Of those, 17.9 million are diagnosed and 5.7 million are undiagnosed. Ninety to 95 percent of people with diabetes have type 2 diabetes. Diabetes is the main cause of kidney failure, limb amputation, and new-onset blindness in American adults.

Sexually transmitted infections

U.S. propaganda poster Fool the Axis Use Prophylaxis, 1942

Sexually transmitted infections (STIs), such as syphilis and HIV, are common but preventable with safe-sex practices. STIs can be asymptomatic, or cause a range of symptoms. Preventive measures for STIs are called prophylactics. The term especially applies to the use of condoms, which are highly effective at preventing disease, but also to other devices meant to prevent STIs, such as dental dams and latex gloves. Other means for preventing STIs include education on how to use condoms or other such barrier devices, testing partners before having unprotected sex, receiving regular STI screenings, to both receive treatment and prevent spreading STIs to partners, and, specifically for HIV, regularly taking prophylactic antiretroviral drugs, such as Truvada. Post-exposure prophylaxis, started within 72 hours (optimally less than 1 hour) after exposure to high-risk fluids, can also protect against HIV transmission.

Malaria prevention using genetic modification

Genetically modified mosquitoes are being used in developing countries to control malaria. This approach has been subject to objections and controversy.

Thrombosis

Thrombosis is a serious circulatory disease affecting thousands, usually older persons undergoing surgical procedures, women taking oral contraceptives and travelers. Consequences of thrombosis can be heart attacks and strokes. Prevention can include: exercise, anti-embolism stockings, pneumatic devices, and pharmacological treatments.

Cancer

In recent years, cancer has become a global problem. Low and middle income countries share a majority of the cancer burden largely due to exposure to carcinogens resulting from industrialization and globalization. However, primary prevention of cancer and knowledge of cancer risk factors can reduce over one third of all cancer cases. Primary prevention of cancer can also prevent other diseases, both communicable and non-communicable, that share common risk factors with cancer.

Lung cancer

Distribution of lung cancer in the United States

Lung cancer is the leading cause of cancer-related deaths in the United States and Europe and is a major cause of death in other countries. Tobacco is an environmental carcinogen and the major underlying cause of lung cancer. Between 25% and 40% of all cancer deaths and about 90% of lung cancer cases are associated with tobacco use. Other carcinogens include asbestos and radioactive materials. Both smoking and second-hand exposure from other smokers can lead to lung cancer and eventually death. Therefore, prevention of tobacco use is paramount to prevention of lung cancer. 

Individual, community, and statewide interventions can prevent or cease tobacco use. 90% of adults in the US who have ever smoked did so prior to the age of 20. In-school prevention/educational programs, as well as counseling resources, can help prevent and cease adolescent smoking. Other cessation techniques include group support programs, nicotine replacement therapy (NRT), hypnosis, and self-motivated behavioral change. Studies have shown long term success rates (>1 year) of 20% for hypnosis and 10%-20% for group therapy.

Cancer screening programs serve as effective sources of secondary prevention. The Mayo Clinic, Johns Hopkins, and Memorial Sloan-Kettering hospitals conducted annual x-ray screenings and sputum cytology tests and found that lung cancer was detected at higher rates, earlier stages, and had more favorable treatment outcomes, which supports widespread investment in such programs.

Legislation can also affect smoking prevention and cessation. In 1992, Massachusetts (United States) voters passed a bill adding an extra 25 cent tax to each pack of cigarettes, despite intense lobbying and $7.3 million spent by the tobacco industry to oppose this bill. Tax revenue goes toward tobacco education and control programs and has led to a decline of tobacco use in the state.

Lung cancer and tobacco smoking are increasing worldwide, especially in China. China is responsible for about one-third of the global consumption and production of tobacco products. Tobacco control policies have been ineffective as China is home to 350 million regular smokers and 750 million passive smokers and the annual death toll is over 1 million. Recommended actions to reduce tobacco use include: decreasing tobacco supply, increasing tobacco taxes, widespread educational campaigns, decreasing advertising from the tobacco industry, and increasing tobacco cessation support resources. In Wuhan, China, a 1998 school-based program implemented an anti-tobacco curriculum for adolescents and reduced the number of regular smokers, though it did not significantly decrease the number of adolescents who initiated smoking. This program was therefore effective in secondary but not primary prevention and shows that school-based programs have the potential to reduce tobacco use.

Skin cancer

An image of melanoma, one of the deadliest forms of skin cancer

Skin cancer is the most common cancer in the United States. The most lethal form of skin cancer, melanoma, leads to over 50,000 annual deaths in the United States. Childhood prevention is particularly important because a significant portion of ultraviolet radiation exposure from the sun occurs during childhood and adolescence and can subsequently lead to skin cancer in adulthood. Furthermore, childhood prevention can lead to the development of healthy habits that continue to prevent cancer for a lifetime.

The Centers for Disease Control and Prevention (CDC) recommends several primary prevention methods including: limiting sun exposure between 10 AM and 4 PM, when the sun is strongest, wearing tighter-weave natural cotton clothing, wide-brim hats, and sunglasses as protective covers, using sunscreens that protect against both UV-A and UV-B rays, and avoiding tanning salons. Sunscreen should be reapplied after sweating, exposure to water (through swimming for example) or after several hours of sun exposure. Since skin cancer is very preventable, the CDC recommends school-level prevention programs including preventive curricula, family involvement, participation and support from the school's health services, and partnership with community, state, and national agencies and organizations to keep children away from excessive UV radiation exposure.

Most skin cancer and sun protection data comes from Australia and the United States. An international study reported that Australians tended to demonstrate higher knowledge of sun protection and skin cancer knowledge, compared to other countries. Of children, adolescents, and adults, sunscreen was the most commonly used skin protection. However, many adolescents purposely used sunscreen with a low sun protection factor (SPF) in order to get a tan. Various Australian studies have shown that many adults failed to use sunscreen correctly; many applied sunscreen well after their initial sun exposure and/or failed to reapply when necessary. A 2002 case-control study in Brazil showed that only 3% of case participants and 11% of control participants used sunscreen with SPF >15.

Cervical cancer

The presence of cancer (adenocarcinoma) detected on a Pap test

Cervical cancer ranks among the top three most common cancers among women in Latin America, sub-Saharan Africa, and parts of Asia. Cervical cytology screening aims to detect abnormal lesions in the cervix so that women can undergo treatment prior to the development of cancer. Given that high quality screening and follow-up care has been shown to reduce cervical cancer rates by up to 80%, most developed countries now encourage sexually active women to undergo a Pap test every 3–5 years. Finland and Iceland have developed effective organized programs with routine monitoring and have managed to significantly reduce cervical cancer mortality while using fewer resources than unorganized, opportunistic programs such as those in the United States or Canada.

In developing nations in Latin America, such as Chile, Colombia, Costa Rica, and Cuba, both public and privately organized programs have offered women routine cytological screening since the 1970s. However, these efforts have not resulted in a significant change in cervical cancer incidence or mortality in these nations. This is likely due to low quality, inefficient testing. However, Puerto Rico, which has offered early screening since the 1960s, has witnessed almost a 50% decline in cervical cancer incidence and almost a four-fold decrease in mortality between 1950 and 1990. Brazil, Peru, India, and several high-risk nations in sub-Saharan Africa which lack organized screening programs, have a high incidence of cervical cancer.

Colorectal cancer

Colorectal cancer is globally the second most common cancer in women and the third-most common in men, and the fourth most common cause of cancer death after lung, stomach, and liver cancer, having caused 715,000 deaths in 2010.

It is also highly preventable; about 80 percent of colorectal cancers begin as benign growths, commonly called polyps, which can be easily detected and removed during a colonoscopy. Other methods of screening for polyps and cancers include fecal occult blood testing. Lifestyle changes that may reduce the risk of colorectal cancer include increasing consumption of whole grains, fruits and vegetables, and reducing consumption of red meat.

Health disparities and barriers to accessing care

Access to healthcare and preventive health services is unequal, as is the quality of care received. A study conducted by the Agency for Healthcare Research and Quality (AHRQ) revealed health disparities in the United States. In the United States, elderly adults (>65 years old) received worse care and had less access to care than their younger counterparts. The same trends are seen when comparing all racial minorities (black, Hispanic, Asian) to white patients, and low-income people to high-income people. Common barriers to accessing and utilizing healthcare resources included lack of income and education, language barriers, and lack of health insurance. Minorities were less likely than whites to possess health insurance, as were individuals who completed less education. These disparities made it more difficult for the disadvantaged groups to have regular access to a primary care provider, receive immunizations, or receive other types of medical care. Additionally, uninsured people tend to not seek care until their diseases progress to chronic and serious states and they are also more likely to forgo necessary tests, treatments, and filling prescription medications.

These sorts of disparities and barriers exist worldwide as well. Often, there are decades of gaps in life expectancy between developing and developed countries. For example, Japan has an average life expectancy that is 36 years greater than that in Malawi. Low-income countries also tend to have fewer physicians than high-income countries. In Nigeria and Myanmar, there are fewer than 4 physicians per 100,000 people while Norway and Switzerland have a ratio that is ten-fold higher. Common barriers worldwide include lack of availability of health services and healthcare providers in the region, great physical distance between the home and health service facilities, high transportation costs, high treatment costs, and social norms and stigma toward accessing certain health services.

Economics of lifestyle-based prevention

With lifestyle factors such as diet and exercise rising to the top of preventable death statistics, the economics of healthy lifestyle is a growing concern. There is little question that positive lifestyle choices provide an investment in health throughout life. To gauge success, traditional measures such as the quality years of life method (QALY), show great value. However, that method does not account for the cost of chronic conditions or future lost earnings because of poor health.[65] Developing future economic models that would guide both private and public investments as well as drive future policy to evaluate the efficacy of positive lifestyle choices on health is a major topic for economists globally. 

Americans spend over three trillion a year on health care but have a higher rate of infant mortality, shorter life expectancies, and a higher rate of diabetes than other high-income nations because of negative lifestyle choices. Despite these large costs, very little is spent on prevention for lifestyle-caused conditions in comparison. The Journal of the American Medical Association estimates that $101 billion was spent in 2013 on the preventable disease of diabetes, and another $88 billion was spent on heart disease. In an effort to encourage healthy lifestyle choices, workplace wellness programs are on the rise; but the economics and effectiveness data are still continuing to evolve and develop.

Health insurance coverage impacts lifestyle choices. In a study by Sudano and Baker, even intermittent loss of coverage has negative effects on healthy choices. The potential repeal of the Affordable Care Act (ACA) could significantly impact coverage for many Americans, as well as “The Prevention and Public Health Fund” which is our nation's first and only mandatory funding stream dedicated to improving the public's health. Also covered in the ACA is counseling on lifestyle prevention issues, such as weight management, alcohol use, and treatment for depression. Policy makers can have substantial effects on the lifestyle choices made by Americans.

Because chronic illnesses predominate as a cause of death in the US and pathways for treating chronic illnesses are complex and multifaceted, prevention is a best practice approach to chronic disease when possible. In many cases, prevention requires mapping complex pathways to determine the ideal point for intervention. Cost-effectiveness of prevention is achievable, but impacted by the length of time it takes to see effects/outcomes of intervention. This makes prevention efforts difficult to fund—particularly in strained financial contexts. Prevention potentially creates other costs as well, due to extending the lifespan and thereby increasing opportunities for illness. In order to assess the cost-effectiveness of prevention, the cost of the preventive measure, savings from avoiding morbidity, and the cost from extending the lifespan need to be considered. Life extension costs become smaller when accounting for savings from postponing the last year of life, which makes up a large fraction of lifetime medical expenditures and becomes cheaper with age. Prevention leads to savings only if the cost of the preventive measure is less than the savings from avoiding morbidity net of the cost of extending the life span. In order to establish reliable economics of prevention for illnesses that are complicated in origin, knowing how best to assess prevention efforts, i.e. developing useful measures and appropriate scope, is required.

Effectiveness

Overview
There is no general consensus as to whether or not preventive healthcare measures are cost-effective, but they increase the quality of life dramatically. There are varying views on what constitutes a "good investment." Some argue that preventive health measures should save more money than they cost, when factoring in treatment costs in the absence of such measures. Others argue in favor of "good value" or conferring significant health benefits even if the measures do not save money. Furthermore, preventive health services are often described as one entity though they comprise a myriad of different services, each of which can individually lead to net costs, savings, or neither. Greater differentiation of these services is necessary to fully understand both the financial and health effects.

A 2010 study reported that in the United States, vaccinating children, cessation of smoking, daily prophylactic use of aspirin, and screening of breast and colorectal cancers had the most potential to prevent premature death. Preventive health measures that resulted in savings included vaccinating children and adults, smoking cessation, daily use of aspirin, and screening for issues with alcoholism, obesity, and vision failure. These authors estimated that if usage of these services in the United States increased to 90% of the population, there would be net savings of $3.7 billion, which comprised only about -0.2% of the total 2006 United States healthcare expenditure. Despite the potential for decreasing healthcare spending, utilization of healthcare resources in the United States still remains low, especially among Latinos and African-Americans. Overall, preventive services are difficult to implement because healthcare providers have limited time with patients and must integrate a variety of preventive health measures from different sources.

While these specific services bring about small net savings not every preventive health measure saves more than it costs. A 1970s study showed that preventing heart attacks by treating hypertension early on with drugs actually did not save money in the long run. The money saved by evading treatment from heart attack and stroke only amounted to about a quarter of the cost of the drugs. Similarly, it was found that the cost of drugs or dietary changes to decrease high blood cholesterol exceeded the cost of subsequent heart disease treatment. Due to these findings, some argue that rather than focusing healthcare reform efforts exclusively on preventive care, the interventions that bring about the highest level of health should be prioritized.

Cohen et al. (2008) outline a few arguments made by skeptics of preventive healthcare. Many argue that preventive measures only cost less than future treatment when the proportion of the population that would become ill in the absence of prevention is fairly large. The Diabetes Prevention Program Research Group conducted a 2012 study evaluating the costs and benefits (in quality-adjusted life-years or QALYs) of lifestyle changes versus taking the drug metformin. They found that neither method brought about financial savings, but were cost-effective nonetheless because they brought about an increase in QALYs. In addition to scrutinizing costs, preventive healthcare skeptics also examine efficiency of interventions. They argue that while many treatments of existing diseases involve use of advanced equipment and technology, in some cases, this is a more efficient use of resources than attempts to prevent the disease. Cohen et al. (2008) suggest that the preventive measures most worth exploring and investing in are those that could benefit a large portion of the population to bring about cumulative and widespread health benefits at a reasonable cost.
Cost-effectiveness of childhood obesity interventions
There are at least four nationally implemented childhood obesity interventions in the United States: the Sugar-Sweetened Beverage excise tax (SSB), the TV AD program, active physical education (Active PE) policies, and early care and education (ECE) policies. They each have similar goals of reducing childhood obesity. The effects of these interventions on BMI have been studied, and the cost-effectiveness analysis (CEA) has led to a better understanding of projected cost reductions and improved health outcomes. The Childhood Obesity Intervention Cost-Effectiveness Study (CHOICES) was conducted to evaluate and compare the CEA of these four interventions.

Gortmaker, S.L. et al. (2015) states: "The four initial interventions were selected by the investigators to represent a broad range of nationally scalable strategies to reduce childhood obesity using a mix of both policy and programmatic strategies... 1. an excise tax of $0.01 per ounce of sweetened beverages, applied nationally and administered at the state level (SSB), 2. elimination of the tax deductibility of advertising costs of TV advertisements for "nutritionally poor" foods and beverages seen by children and adolescents (TV AD), 3. state policy requiring all public elementary schools in which physical education (PE) is currently provided to devote ≥50% of PE class time to moderate and vigorous physical activity (Active PE), and 4. state policy to make early child educational settings healthier by increasing physical activity, improving nutrition, and reducing screen time (ECE)." 

The CHOICES found that SSB, TV AD, and ECE led to net cost savings. Both SSB and TV AD increased quality adjusted life years and produced yearly tax revenue of 12.5 billion US dollars and 80 million US dollars, respectively.

Some challenges with evaluating the effectiveness of child obesity interventions include:
  1. The economic consequences of childhood obesity are both short and long term. In the short term, obesity impairs cognitive achievement and academic performance. Some believe this is secondary to negative effects on mood or energy, but others suggest there may be physiological factors involved. Furthermore, obese children have increased health care expenses (e.g. medications, acute care visits). In the long term, obese children tend to become obese adults with associated increased risk for a chronic condition such as diabetes or hypertension. Any effect on their cognitive development may also affect their contributions to society and socioeconomic status.
  2. In the CHOICES, it was noted that translating the effects of these interventions may in fact differ among communities throughout the nation. In addition it was suggested that limited outcomes are studied and these interventions may have an additional effect that is not fully appreciated.
  3. Modeling outcomes in such interventions in children over the long term is challenging because advances in medicine and medical technology are unpredictable. The projections from cost-effective analysis may need to be reassessed more frequently.

The economics of preventive care in the US
The cost-effectiveness of preventive care is a highly debated topic. While some economists argue that preventive care is valuable and potentially cost saving, others believe it is an inefficient waste of resources.[91] Preventive care is composed of a variety of clinical services and programs including annual doctor's check-ups, annual immunizations, and wellness programs; recent models show that these simple interventions can have significant economic impacts.

Clinical preventive services & programs

Research on preventive care addresses the question of whether it is cost saving or cost effective and whether there is an economics evidence base for health promotion and disease prevention. The need for and interest in preventive care is driven by the imperative to reduce health care costs while improving quality of care and the patient experience. Preventive care can lead to improved health outcomes and cost savings potential. Services such as health assessments/screenings, prenatal care, and telehealth and telemedicine can reduce morbidity or mortality with low cost or cost savings. Specifically, health assessments/screenings have cost savings potential, with varied cost-effectiveness based on screening and assessment type. Inadequate prenatal care can lead to an increased risk of prematurity, stillbirth, and infant death. Time is the ultimate resource and preventive care can help mitigate the time costs. Telehealth and telemedicine is one option that has gained consumer interest, acceptance and confidence and can improve quality of care and patient satisfaction.

Understanding the economics for investment

There are benefits and trade-offs when considering investment in preventive care versus other types of clinical services. Preventive care can be a good investment as supported by the evidence base and can drive population health management objectives. The concepts of cost saving and cost-effectiveness are different and both are relevant to preventive care. For example, preventive care that may not save money may still provide health benefits. Thus, there is a need to compare interventions relative to impact on health and cost.

Preventive care transcends demographics and is applicable to people of every age. The Health Capital Theory underpins the importance of preventive care across the lifecycle and provides a framework for understanding the variances in health and health care that are experienced. It treats health as a stock that provides direct utility. Health depreciates with age and the aging process can be countered through health investments. The theory further supports that individuals demand good health, that the demand for health investment is a derived demand (i.e. investment is health is due to the underlying demand for good health), and the efficiency of the health investment process increases with knowledge (i.e. it is assumed that the more educated are more efficient consumers and producers of health).

The prevalence elasticity of demand for prevention can also provide insights into the economics. Demand for preventive care can alter the prevalence rate of a given disease and further reduce or even reverse any further growth of prevalence. Reduction in prevalence subsequently leads to reduction in costs. 

Economics for policy action

There are a number of organizations and policy actions that are relevant when discussing the economics of preventive care services. The evidence base, viewpoints, and policy briefs from the Robert Wood Johnson Foundation, the Organisation for Economic Co-operation and Development (OECD), and efforts by the U.S. Preventive Services Task Force (USPSTF) all provide examples that improve the health and well-being of populations (e.g. preventive health assessments/screenings, prenatal care, and telehealth/telemedicine). The Patient Protection and Affordable Care Act (PPACA, ACA) has major influence on the provision of preventive care services, although it is currently under heavy scrutiny and review by the new administration. According to the Centers for Disease Control and Prevention (CDC), the ACA makes preventive care affordable and accessible through mandatory coverage of preventive services without a deductible, copayment, coinsurance, or other cost sharing.

The U.S. Preventive Services Task Force (USPSTF), a panel of national experts in prevention and evidence-based medicine, works to improve health of Americans by making evidence-based recommendations about clinical preventive services. They do not consider the cost of a preventive service when determining a recommendation. Each year, the organization delivers a report to Congress that identifies critical evidence gaps in research and recommends priority areas for further review.

The National Network of Perinatal Quality Collaboratives (NNPQC), sponsored by the CDC, supports state-based perinatal quality collaboratives (PQCs) in measuring and improving upon health care and health outcomes for mothers and babies. These PQCs have contributed to improvements such as reduction in deliveries before 39 weeks, reductions in healthcare associated blood stream infections, and improvements in the utilization of antenatal corticosteroids.

Telehealth and telemedicine has realized significant growth and development recently. The Center for Connected Health Policy (The National Telehealth Policy Resource Center) has produced multiple reports and policy briefs on the topic of Telehealth and Telemedicine and how they contribute to preventive services.

Policy actions and provision of preventive services do not guarantee utilization. Reimbursement has remained a significant barrier to adoption due to variances in payer and state level reimbursement policies and guidelines through government and commercial payers. Americans use preventive services at about half the recommended rate and cost-sharing, such as deductibles, co-insurance, or copayments, also reduce the likelihood that preventive services will be used. Further, despite the ACA's enhancement of Medicare benefits and preventive services, there were no effects on preventive service utilization, calling out the fact that other fundamental barriers exist.
The Affordable Care Act and preventive healthcare
The Patient Protection and Affordable Care Act, also known as just the Affordable Care Act or Obamacare, was passed and became law in the United States on March 23, 2010. The finalized and newly ratified law was to address many issues in the U.S. healthcare system, which included expansion of coverage, insurance market reforms, better quality, and the forecast of efficiency and costs. Under the insurance market reforms the act required that insurance companies no longer exclude people with pre-existing conditions, allow for children to be covered on their parents' plan until the age of 26, and expand appeals that dealt with reimbursement denials. The Affordable Care Act also banned the limited coverage imposed by health insurances, and insurance companies were to include coverage for preventive health care services. The U.S. Preventive Services Task Force has categorized and rated preventive health services as either ‘”A” or “B”, as to which insurance companies must comply and present full coverage. Not only has the U.S. Preventive Services Task Force provided graded preventive health services that are appropriate for coverage, they have also provided many recommendations to clinicians and insurers to promote better preventive care to ultimately provide better quality of care and lower the burden of costs.

Health insurance and preventive care
 
Healthcare insurance companies are willing to pay for preventive care despite the fact that patients are not acutely sick in hope that it will prevent them from developing a chronic disease later on in life. Today, health insurance plans offered through the Marketplace, mandated by the Affordable Care Act are required to provide certain preventive care services free of charge to patients. Section 2713 of the Affordable Care Act, specifies that all private Marketplace and all employer-sponsored private plans (except those grandfathered in) are required to cover preventive care services that are ranked A or B by the US Preventive Services Task Force free of charge to patients. For example, UnitedHealthcare insurance company has published patient guidelines at the beginning of the year explaining their preventive care coverage.

Evaluating incremental benefits of preventive care
 
Evaluating the incremental benefits of preventive care requires a longer period of time when compared to acutely ill patients. Inputs into the model such as discounting rate and time horizon can have significant effects on the results. One controversial subject is use of a 10-year time frame to assess cost effectiveness of diabetes preventive services by the Congressional Budget Office.

The preventive care services mainly focus on chronic disease. The Congressional Budget Office has provided guidance that further research is needed in the area of the economic impacts of obesity in the US before the CBO can estimate budgetary consequences. A bipartisan report published in May 2015 recognizes the potential of preventive care to improve patients' health at individual and population levels while decreasing the healthcare expenditure.

An economic case for preventive health
Mortality from modifiable risk factors
Chronic diseases such as heart disease, stroke, diabetes, obesity and cancer have become the most common and costly health problems in the United States. In 2014, it was projected that by 2023 that the number of chronic disease cases would increase by 42%, resulting in $4.2 trillion in treatment and lost economic output. They are also among the top ten leading causes of mortality. Chronic diseases are driven by risk factors that are largely preventable. Sub-analysis performed on all deaths in the United States in the year 2000 revealed that almost half were attributed to preventable behaviors including tobacco, poor diet, physical inactivity and alcohol consumption. More recent analysis reveals that heart disease and cancer alone accounted for nearly 46% of all deaths. Modifiable risk factors are also responsible for a large morbidity burden, resulting in poor quality of life in the present and loss of future life earning years. It is further estimated that by 2023, focused efforts on the prevention and treatment of chronic disease may result in 40 million fewer chronic disease cases, potentially reducing treatment costs by $220 billion.

Childhood vaccinations reduce health care costs

Childhood immunizations are largely responsible for the increase in life expectancy in the 20th century. From an economic standpoint, childhood vaccines demonstrate a very high return on investment. According to Healthy People 2020, for every birth cohort that receives the routine childhood vaccination schedule, direct health care costs are reduced by $9.9 billion and society saves $33.4 billion in indirect costs. The economic benefits of childhood vaccination extend beyond individual patients to insurance plans and vaccine manufacturers, all while improving the health of the population.

Prevention and health capital theory

The burden of preventable illness extends beyond the healthcare sector, incurring significant costs related to lost productivity among workers in the workforce. Indirect costs related to poor health behaviors and associated chronic disease costs U.S. employers billions of dollars each year.

According to the American Diabetes Association (ADA), medical costs for employees with diabetes are twice as high as for workers without diabetes and are caused by work-related absenteeism ($5 billion), reduced productivity at work ($20.8 billion), inability to work due to illness-related disability ($21.6 billion), and premature mortality ($18.5 billion). Reported estimates of the cost burden due to increasingly high levels of overweight and obese members in the workforce vary, with best estimates suggesting 450 million more missed work days, resulting in $153 billion each year in lost productivity, according to the CDC Healthy Workforce.

In the field of economics, the Health Capital model explains how individual investments in health can increase earnings by “increasing the number of healthy days available to work and to earn income.” In this context, health can be treated both as a consumption good, wherein individuals desire health because it improves quality of life in the present, and as an investment good because of its potential to increase attendance and workplace productivity over time. Preventive health behaviors such as healthful diet, regular exercise, access to and use of well-care, avoiding tobacco, and limiting alcohol can be viewed as health inputs that result in both a healthier workforce and substantial cost savings.

Preventive care and quality adjusted life years.
 
Health benefits of preventive care measures can be described in terms of quality-adjusted life-years (QALYs) saved. A QALY takes into account length and quality of life, and is used to evaluate the cost-effectiveness of medical and preventive interventions. Classically, one year of perfect health is defined as 1 QALY and a year with any degree of less than perfect health is assigned a value between 0 and 1 QALY. As an economic weighting system, the QALY can be used to inform personal decisions, to evaluate preventive interventions and to set priorities for future preventive efforts. 

Cost-saving and cost-effective benefits of preventive care measures are well established. The Robert Wood Johnson Foundation evaluated the prevention cost-effectiveness literature, and found that many preventive measures meet the benchmark of <$100,000 per QALY and are considered to be favorably cost-effective. These include screenings for HIV and chlamydia, cancers of the colon, breast and cervix, vision screening, and screening for abdominal aortic aneurysms in men >60 in certain populations. Alcohol and tobacco screening were found to be cost-saving in some reviews and cost-effective in others. According to the RWJF analysis, two preventive interventions were found to save costs in all reviews: childhood immunizations and counseling adults on the use of aspirin.

Prevention in minority populations

Health disparities are increasing in the United States for chronic diseases such as obesity, diabetes, cancer, and cardiovascular disease. Populations at heightened risk for health inequities are the growing proportion of racial and ethnic minorities, including African Americans, American Indians, Hispanics/Latinos, Asian Americans, Alaska Natives and Pacific Islanders.

According to the Racial and Ethnic Approaches to Community Health (REACH), a national CDC program, non-Hispanic blacks currently have the highest rates of obesity (48%), and risk of newly diagnosed diabetes is 77% higher among non-Hispanic blacks, 66% higher among Hispanics/Latinos and 18% higher among Asian Americans compared to non-Hispanic whites. Current U.S. population projections predict that more than half of Americans will belong to a minority group by 2044. Without targeted preventive interventions, medical costs from chronic disease inequities will become unsustainable. Broadening health policies designed to improve delivery of preventive services for minority populations may help reduce substantial medical costs caused by inequities in health care, resulting in a return on investment.

Policies of prevention
 
Chronic disease is a population level issue that requires population health level efforts and national and state level public policy to effectively prevent, rather than individual level efforts. The United States currently employs many public health policy efforts aligned with the preventive health efforts discussed above. For instance, the Centers for Disease Control and Prevention support initiatives such as Health in All Policies and HI-5 (Health Impact in 5 Years), collaborative efforts that aim to consider prevention across sectors and address social determinants of health as a method of primary prevention for chronic disease. Specific examples of programs targeting vaccination and obesity prevention in childhood are discussed in the sections to follow. 

Policy prevention of obesity

Policies that address the obesity epidemic should be proactive and far-reaching, including a variety of stakeholders both in healthcare and in other sectors. Recommendations from the Institute of Medicine in 2012 suggest that “…concerted action be taken across and within five environments (physical activity (PA), food and beverage, marketing and messaging, healthcare and worksites, and schools) and all sectors of society (including government, business and industry, schools, child care, urban planning, recreation, transportation, media, public health, agriculture, communities, and home) in order for obesity prevention efforts to truly be successful.”

There are dozens of current policies acting at either (or all of) the federal, state, local and school levels. Most states employ a physical education requirement of 150 minutes of physical education per week at school, a policy of the National Association of Sport and Physical Education. In some cities, including Philadelphia, a sugary food tax is employed. This is a part of an amendment to Title 19 of the Philadelphia Code, “Finance, Taxes and Collections”; Chapter 19-4100, “Sugar-Sweetened Beverage Tax, that was approved 2016, which establishes an excise tax of $0.015 per fluid ounce on distributors of beverages sweetened with both caloric and non-caloric sweeteners. Distributors are required to file a return with the department, and the department can collect taxes, among other responsibilities.

These policies can be a source of tax credits. For example, under the Philadelphia policy, businesses can apply for tax credits with the revenue department on a first-come, first-served basis. This applies until the total amount of credits for a particular year reaches one million dollars.

Recently, advertisements for food and beverages directed at children have received much attention. The Children's Food and Beverage Advertising Initiative (CFBAI) is a self-regulatory program of the food industry. Each participating company makes a public pledge that details its commitment to advertise only foods that meet certain nutritional criteria to children under 12 years old. This is a self-regulated program with policies written by the Council of Better Business Bureaus. The Robert Wood Johnson Foundation funded research to test the efficacy of the CFBAI. The results showed progress in terms of decreased advertising of food products that target children and adolescents.

To explore other programs and initiatives related to policies of childhood obesity, visit the following organizations and online databases: U.S. Department of Agriculture, Robert Wood Johnson Foundation-supported Bridging the Gap Program, National Association of County and City Health Officials, Yale Rudd Center for Food Policy & Obesity, Centers for Disease Control and Prevention's Chronic Disease State Policy Tracking System, National Conference of State Legislatures, Prevention Institute's ENACT local policy database, Organization for Economic Cooperation and Development (OECD), and the U.S. Preventive Services Task Force (USPSTF). 

Childhood immunization policies

Despite nationwide controversies over childhood vaccination and immunization, there are policies and programs at the federal, state, local and school levels outlining vaccination requirements. All states require children to be vaccinated against certain communicable diseases as a condition for school attendance. However, currently 18 states allow exemptions for “philosophical or moral reasons.” Diseases for which vaccinations form part of the standard ACIP vaccination schedule are diphtheria tetanus pertussis (whooping cough), poliomyelitis (polio), measles, mumps, rubella, haemophilus influenzae type b, hepatitis B, influenza, and pneumococcal infections. These schedules can be viewed on the CDC website.

The CDC website describes a federally funded program, Vaccines for Children (VFC), which provides vaccines at no cost to children who might not otherwise be vaccinated because of inability to pay. Additionally, the Advisory Committee on Immunization Practices (ACIP) is an expert vaccination advisory board that informs vaccination policy and guides on-going recommendations to the CDC, incorporating the most up-to-date cost-effectiveness and risk-benefit evidence in its recommendations. 

An economic case conclusion

There are economic and health related arguments for preventive healthcare. Direct and indirect medical costs related to preventable chronic disease are high, and will continue to rise with an aging and increasingly diverse U.S. population. The government, at federal, state, local and school levels has acknowledged this and created programs and policies to support chronic disease prevention, notably at the childhood age, and focusing on obesity prevention and vaccination. Economically, with an increase in QALY and a decrease in lost productivity over a lifetime, existing and innovative prevention interventions demonstrate a high return on investment and are expected to result in substantial healthcare cost-savings over time.

Cure

From Wikipedia, the free encyclopedia

A cure is a substance or procedure that ends a medical condition, such as a medication, a surgical operation, a change in lifestyle or even a philosophical mindset that helps end a person's sufferings; or the state of being healed, or cured. The medical condition could be a disease, mental illness, disability, or simply a condition a person considers socially undesirable, such as baldness or lack of breast tissue.

A disease is said to be incurable if there is always a chance of the patient relapsing, no matter how long the patient has been in remission. An incurable disease may or may not be a terminal illness; conversely, a curable illness can still result in the patient's death.

The proportion of people with a disease that are cured by a given treatment, called the cure fraction or cure rate, is determined by comparing disease-free survival of treated people against a matched control group that never had the disease.

Another way of determining the cure fraction and/or "cure time" is by measuring when the hazard rate in a diseased group of individuals returns to the hazard rate measured in the general population.
Inherent in the idea of a cure is the permanent end to the specific instance of the disease. When a person has the common cold, and then recovers from it, the person is said to be cured, even though the person might someday catch another cold. Conversely, a person that has successfully managed a disease, such as diabetes mellitus, so that it produces no undesirable symptoms for the moment, but without actually permanently ending it, is not cured.

Related concepts, whose meaning can differ, include response, remission and recovery.

Statistical model

In complex diseases, such as cancer, researchers rely on statistical comparisons of disease-free survival (DFS) of patients against matched, healthy control groups. This logically rigorous approach essentially equates indefinite remission with cure. The comparison is usually made through the Kaplan-Meier estimator approach.

The simplest cure rate model was published by Berkson and Gage in 1952. In this model, the survival at any given time is equal to those that are cured plus those that are not cured, but who have not yet died or, in the case of diseases that feature asymptomatic remissions, have not yet re-developed signs and symptoms of the disease. When all of the non-cured people have died or re-developed the disease, only the permanently cured members of the population will remain, and the DFS curve will be perfectly flat. The earliest point in time that the curve goes flat is the point at which all remaining disease-free survivors are declared to be permanently cured. If the curve never goes flat, then the disease is formally considered incurable (with the existing treatments). 

The Berkson and Gage equation is , where is the proportion of people surviving at any given point in time, is the proportion that are permanently cured, and is an exponential curve that represents the survival of the non-cured people. 

Cure rate curves can be determined through an analysis of the data. The analysis allows the statistician to determine the proportion of people that are permanently cured by a given treatment, and also how long after treatment it is necessary to wait before declaring an asymptomatic individual to be cured.

Several cure rate models exist, such as the expectation-maximization algorithm and Markov chain Monte Carlo model. It is possible to use cure rate models to compare the efficacy of different treatments. Generally, the survival curves are adjusted for the effects of normal aging on mortality, especially when diseases of older people are being studied.

From the perspective of the patient, particularly one that has received a new treatment, the statistical model may be frustrating. It may take many years to accumulate sufficient information to determine the point at which the DFS curve flattens (and therefore no more relapses are expected). Some diseases may be discovered to be technically incurable, but also to require treatment so infrequently as to be not materially different from a cure. Other diseases may prove to have multiple plateaus, so that what was once hailed as a "cure" results unexpectedly in very late relapses. Consequently, patients, parents and psychologists developed the notion of psychological cure, or the moment at which the patient decides that the treatment was sufficiently likely to be a cure as to be called a cure. For example, a patient may declare himself to be "cured", and to determine to live his life as if the cure were definitely confirmed, immediately after treatment.

Related terms

Response
is a partial reduction in symptoms after treatment.
Recovery
is a restoration of health or functioning. A person who has been cured may not be fully recovered, and a person who has recovered may not be cured, as in the case of a person in a temporary remission or who is an asymptomatic carrier for an infectious disease.
Prevention
is a way to avoid an injury, sickness, disability, or disease in the first place, and generally it will not help someone who is already ill (though there are exceptions). For instance, many babies and young children are vaccinated against polio and other infectious diseases, which prevents them from contracting polio. But the vaccination does not work on patients who already have polio. A treatment or cure is applied after a medical problem has already started.
Therapy
treats a problem, and may or may not lead to its cure. In incurable conditions, a treatment ameliorates the medical condition, often only for as long as the treatment is continued or for a short while after treatment is ended. For example, there is no cure for AIDS, but treatments are available to slow down the harm done by HIV and extend the treated person's life. Treatments don't always work. For example, chemotherapy is a treatment for cancer, but it may not work for every patient. In easily cured forms of cancer, such as childhood leukemias, testicular cancer and Hodgkin lymphoma, cure rates may approach 90%. In other forms, treatment may be essentially impossible. A treatment need not be successful in 100% of patients to be considered curative. A given treatment may permanently cure only a small number of patients; so long as those patients are cured, the treatment is considered curative.

Examples

Cures can take the form of natural antibiotics (for bacterial infections), synthetic antibiotics such as the sulphonamides, or fluoroquinolones, antivirals (for a very few viral infections), antifungals, antitoxins, vitamins, gene therapy, surgery, chemotherapy, radiotherapy, and so on. Despite a number of cures being developed, the list of incurable diseases remains long.

1700s

Scurvy became curable (as well as preventable) with doses of vitamin C (for example, in limes) when James Lind published A Treatise on the Scurvy (1753).

1890s

Antitoxins to diphtheria and tetanus toxins were produced by Emil Adolf von Behring and his colleagues from 1890 onwards. The use of diphtheria antitoxin for the treatment of diphtheria was regarded by The Lancet as the "most important advance of the [19th] Century in the medical treatment of acute infectious disease".

1930s

Sulphonamides become the first widely available cure for bacterial infections.

1940s

Bacterial infections became easily curable with the development of antibiotics.

1950s

Leukemia and other blood cell disorders such as sickle cell anaemia became curable when E. Donnall Thomas performed the first bone marrow transplant in 1956

2000s

HIV became curable (through a very dangerous procedure) when a bone marrow transplant (using a donor with a rare variant of a cell surface receptor) was performed on Timothy Ray Brown. A similar successful operation was performed in 2017.

2010s

Hepatitis C, a viral infection, became curable through treatment with antiviral medications.

X-linked severe combined immunodeficiency disorder, also known as bubble boy disease, became curable through gene therapy

Guillain–Barré syndrome

From Wikipedia, the free encyclopedia
  
Guillain–Barré syndrome
Other namesGuillain–Barré–Strohl syndrome, Landry's paralysis, postinfectious polyneuritis[1]
Spirodoc FVC.jpg
A handheld spirometry device, which can be used to anticipate breathing complications of Guillain–Barré syndrome
Pronunciation
SpecialtyNeurology
SymptomsMuscle weakness beginning in the feet and hands
ComplicationsBreathing difficulties, heart and blood pressure problems
Usual onsetRapid (hours to weeks)
CausesUnknown
Diagnostic methodBased on symptoms, nerve conduction studies, lumbar puncture
TreatmentSupportive care, intravenous immunoglobulin, plasmapheresis
PrognosisWeeks to years for recovery
Frequency2 per 100,000 people per year
Deaths7.5% of those affected

Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. The initial symptoms are typically changes in sensation or pain along with muscle weakness, beginning in the feet and hands, often spreading to the arms and upper body, with both sides being involved. The symptoms may develop over hours to a few weeks. During the acute phase, the disorder can be life-threatening, with about 15 percent of people developing weakness of the breathing muscles and, therefore, requiring mechanical ventilation. Some are affected by changes in the function of the autonomic nervous system, which can lead to dangerous abnormalities in heart rate and blood pressure.

Although the cause is unknown, the underlying mechanism involves an autoimmune disorder in which the body's immune system mistakenly attacks the peripheral nerves and damages their myelin insulation. Sometimes this immune dysfunction is triggered by an infection or, less commonly by surgery and rarely by vaccination. The diagnosis is usually made based on the signs and symptoms, through the exclusion of alternative causes, and supported by tests such as nerve conduction studies and examination of the cerebrospinal fluid. There are a number of subtypes based on the areas of weakness, results of nerve conduction studies and the presence of certain antibodies. It is classified as an acute polyneuropathy.

In those with severe weakness, prompt treatment with intravenous immunoglobulins or plasmapheresis, together with supportive care, will lead to good recovery in the majority of people. Recovery may take weeks to years, with about a third having some permanent weakness. Globally, death occurs in about 7.5% of those affected. Guillain–Barré syndrome is rare, at one or two cases per 100,000 people every year. Both sexes and all parts of the world have similar rates of disease. The syndrome is named after the French neurologists Georges Guillain and Jean Alexandre Barré, who, together with French physician André Strohl, described the condition in 1916.

Signs and symptoms

The first symptoms of Guillain–Barré syndrome are numbness, tingling, and pain, alone or in combination. This is followed by weakness of the legs and arms that affects both sides equally and worsens over time. The weakness can take half a day to over two weeks to reach maximum severity, and then becomes steady. In one in five people, the weakness continues to progress for as long as four weeks. The muscles of the neck may also be affected, and about half experience involvement of the cranial nerves which supply the head and face; this may lead to weakness of the muscles of the face, swallowing difficulties and sometimes weakness of the eye muscles. In 8%, the weakness affects only the legs (paraplegia or paraparesis). Involvement of the muscles that control the bladder and anus is unusual. In total, about a third of people with Guillain–Barré syndrome continue to be able to walk. Once the weakness has stopped progressing, it persists at a stable level ("plateau phase") before improvement occurs. The plateau phase can take between two days and six months, but the most common duration is a week. Pain-related symptoms affect more than half, and include back pain, painful tingling, muscle pain and pain in the head and neck relating to irritation of the lining of the brain.

Many people with Guillain–Barré syndrome have experienced the signs and symptoms of an infection in the 3–6 weeks prior to the onset of the neurological symptoms. This may consist of upper respiratory tract infection (rhinitis, sore throat) or diarrhea.

In children, particularly those younger than six years old, the diagnosis can be difficult and the condition is often initially mistaken (sometimes for up to two weeks) for other causes of pains and difficulty walking, such as viral infections, or bone and joint problems.

On neurological examination, characteristic features are the reduced strength of muscles and reduced or absent tendon reflexes (hypo- or areflexia, respectively). However, a small proportion have normal reflexes in affected limbs before developing areflexia, and some may have exaggerated reflexes. In the Miller Fisher variant of Guillain–Barré syndrome (see below), a triad of weakness of the eye muscles, abnormalities in coordination, as well as absent reflexes can be found. The level of consciousness is normally unaffected in Guillain–Barré syndrome, but the Bickerstaff brainstem encephalitis subtype may feature drowsiness, sleepiness, or coma.

Respiratory failure

A quarter of all people with Guillain–Barré syndrome develop weakness of the breathing muscles leading to respiratory failure, the inability to breathe adequately to maintain healthy levels of oxygen and/or carbon dioxide in the blood. This life-threatening scenario is complicated by other medical problems such as pneumonia, severe infections, blood clots in the lungs and bleeding in the digestive tract in 60% of those who require artificial ventilation.

Autonomic dysfunction

The autonomic or involuntary nervous system, which is involved in the control of body functions such as heart rate and blood pressure, is affected in two thirds of people with Guillain–Barré syndrome, but the impact is variable. Twenty percent may experience severe blood-pressure fluctuations and irregularities in the heart beat, sometimes to the point that the heart beat stops and requiring pacemaker-based treatment. Other associated problems are abnormalities in perspiration and changes in the reactivity of the pupils. Autonomic nervous system involvement can affect even those who do not have severe muscle weakness.

Causes

A scanning electron microscope-derived image of Campylobacter jejuni, which triggers about 30% of cases of Guillain–Barré syndrome

Two thirds of people with Guillain–Barré syndrome have experienced an infection before the onset of the condition. Most commonly these are episodes of gastroenteritis or a respiratory tract infection. In many cases, the exact nature of the infection can be confirmed. Approximately 30% of cases are provoked by Campylobacter jejuni bacteria, which cause diarrhea. A further 10% are attributable to cytomegalovirus (CMV, HHV-5). Despite this, only very few people with Campylobacter or CMV infections develop Guillain–Barré syndrome (0.25–0.65 per 1000 and 0.6–2.2 per 1000 episodes, respectively). The strain of Campylobacter involved may determine the risk of GBS; different forms of the bacteria have different lipopolysaccharides on their surface, and some may induce illness (see below) while others will not.

Links between other infections and GBS are less certain. Two other herpesviruses (Epstein–Barr virus/HHV-4 and varicella zoster virus/HHV-3) and the bacterium Mycoplasma pneumoniae have been associated with GBS. The tropical viral infection dengue fever and Zika virus have also been associated with episodes of GBS. Previous hepatitis E virus infection has been found to be more common in people with Guillain–Barré syndrome.

Some cases may be triggered by the influenza virus and potentially influenza vaccine. An increased incidence of Guillain–Barré syndrome followed influenza immunization that followed the 1976 swine flu outbreak (H1N1 A/NJ/76); 8.8 cases per million recipients developed the complication. Since then, close monitoring of cases attributable to vaccination has demonstrated that influenza itself can induce GBS. Small increases in incidence have been observed in subsequent vaccination campaigns, but not to the same extent. The 2009 flu pandemic vaccine (against pandemic swine flu virus H1N1/PDM09) did not cause a significant increase in cases. It is considered that the benefits of vaccination in preventing influenza outweigh the small risks of GBS after vaccination. In fact, natural influenza infection is a stronger risk factor for the development of GBS than is influenza vaccination and getting the vaccination actually reduces the risk of GBS overall by lowering the risk of catching influenza. Even those who have previously experienced Guillain–Barré syndrome are considered safe to receive the vaccine in the future. Nevertheless, in the United States GBS after seasonal influenza vaccination is listed on the federal government's vaccine injury table and compensation may be available through the National Vaccine Injury Compensation Program. Other vaccines, such as those against poliomyelitis, tetanus or measles, have not been associated with a risk of GBS.

Mechanism

Structure of a typical neuron
Neuron
Guillain–Barré syndrome – nerve damage

The nerve dysfunction in Guillain–Barré syndrome is caused by an immune attack on the nerve cells of the peripheral nervous system and their support structures. The nerve cells have their body (the soma) in the spinal cord and a long projection (the axon) that carries electrical nerve impulses to the neuromuscular junction where the impulse is transferred to the muscle. Axons are wrapped in a sheath of Schwann cells that contain myelin. Between Schwann cells are gaps (nodes of Ranvier) where the axon is exposed. Different types of Guillain–Barré syndrome feature different types of immune attack. The demyelinating variant (AIDP, see below) features damage to the myelin sheath by white blood cells (T lymphocytes and macrophages); this process is preceded by activation of a group of blood proteins known as complement. In contrast, the axonal variant is mediated by IgG antibodies and complement against the cell membrane covering the axon without direct lymphocyte involvement.

Various antibodies directed at nerve cells have been reported in Guillain–Barré syndrome. In the axonal subtype, these antibodies have been shown to bind to gangliosides, a group of substances found in peripheral nerves. A ganglioside is a molecule consisting of ceramide bound to a small group of hexose-type sugars and containing various numbers of N-acetylneuraminic acid groups. The key four gangliosides against which antibodies have been described are GM1, GD1a, GT1a, and GQ1b, with different anti-ganglioside antibodies being associated with particular features; for instance, GQ1b antibodies have been linked with Miller Fisher variant GBS and related forms including Bickerstaff encephalitis. The production of these antibodies after an infection is probably the result of molecular mimicry, where the immune system is reacting to microbial substances, but the resultant antibodies also react with substances occurring naturally in the body. After a Campylobacter infection, the body produces antibodies of the IgA class; only a small proportion of people also produce IgG antibodies against bacterial substance cell wall substances (e.g. lipooligosaccharides) that crossreact with human nerve cell gangliosides. It is not currently known how this process escapes central tolerance to gangliosides, which is meant to suppress the production of antibodies against the body's own substances. Not all antiganglioside antibodies cause disease, and it has recently been suggested that some antibodies bind to more than one type of epitope simultaneously (heterodimeric binding) and that this determines the response. Furthermore, the development of pathogenic antibodies may depend on the presence of other strains of bacteria in the bowel.

Diagnosis

The diagnosis of Guillain–Barré syndrome depends on findings such as rapid development of muscle paralysis, absent reflexes, absence of fever, and a likely cause. Cerebrospinal fluid analysis (through a lumbar spinal puncture) and nerve conduction studies are supportive investigations commonly performed in the diagnosis of GBS. Testing for antiganglioside antibodies is often performed, but their contribution to diagnosis is usually limited. Blood tests are generally performed to exclude the possibility of another cause for weakness, such as a low level of potassium in the blood. An abnormally low level of sodium in the blood is often encountered in Guillain–Barré syndrome. This has been attributed to the inappropriate secretion of antidiuretic hormone, leading to relative retention of water.

In many cases, magnetic resonance imaging of the spinal cord is performed to distinguish between Guillain–Barré syndrome and other conditions causing limb weakness, such as spinal cord compression. If an MRI scan shows enhancement of the nerve roots, this may be indicative of GBS. In children, this feature is present in 95% of scans, but it is not specific to Guillain–Barré syndrome, so other confirmation is also needed.

Spinal fluid

Cerebrospinal fluid envelops the brain and the spine, and lumbar puncture or spinal tap is the removal of a small amount of fluid using a needle inserted between the lumbar vertebrae. Characteristic findings in Guillain–Barré syndrome are an elevated protein level, usually greater than 0.55 g/L, and fewer than 10 white blood cells per cubic millimeter of fluid ("albuminocytological dissociation"). This pattern distinguishes Guillain–Barré syndrome from other conditions (such as lymphoma and poliomyelitis) in which both the protein and the cell count are elevated. Elevated CSF protein levels are found in approximately 50% of patients in the first 3 days after onset of weakness, which increases to 80% after the first week.

Repeating the lumbar puncture during the disease course is not recommended. The protein levels may rise after treatment has been administered.

Neurophysiology

Directly assessing nerve conduction of electrical impulses can exclude other causes of acute muscle weakness, as well as distinguish the different types of Guillain–Barré syndrome. Needle electromyography (EMG) and nerve conduction studies may be performed. In the first two weeks, these investigations may not show any abnormality. Neurophysiology studies are not required for the diagnosis.

Formal criteria exist for each of the main subtypes of Guillain–Barré syndrome (AIDP and AMAN/AMSAN, see below), but these may misclassify some cases (particularly where there is reversible conduction failure) and therefore changes to these criteria have been proposed. Sometimes, repeated testing may be helpful.

Clinical subtypes

A number of subtypes of Guillain–Barré syndrome are recognized. Despite this, many people have overlapping symptoms that can make the classification difficult in individual cases. All types have partial forms. For instance, some people experience only isolated eye-movement or coordination problems; these are thought to be a subtype of Miller Fisher syndrome and have similar antiganglioside antibody patterns.

Type Symptoms Population affected Nerve conduction studies Antiganglioside antibodies
Acute inflammatory demyelinating polyneuropathy (AIDP) Sensory symptoms and muscle weakness, often with cranial nerve weakness and autonomic involvement Most common in Europe and North America Demyelinating polyneuropathy No clear association
Acute motor axonal neuropathy (AMAN) Isolated muscle weakness without sensory symptoms in less than 10%; cranial nerve involvement uncommon Rare in Europe and North America, substantial proportion (30-65%) in Asia and Central and South America; sometimes called "Chinese paralytic syndrome" Axonal polyneuropathy, normal sensory action potential GM1a/b, GD1a & GalNac-GD1a
Acute motor and sensory axonal neuropathy (AMSAN) Severe muscle weakness similar to AMAN but with sensory loss - Axonal polyneuropathy, reduced or absent sensory action potential GM1, GD1a
Pharyngeal-cervical-brachial variant Weakness particularly of the throat muscles, and face, neck, and shoulder muscles - Generally normal, sometimes axonal neuropathy in arms Mostly GT1a, occasionally GQ1b, rarely GD1a
Miller Fisher syndrome Ataxia, eye muscle weakness, areflexia but usually no limb weakness This variant occurs more commonly in men than in women (2:1 ratio). Cases typically occur in the spring and the average age of occurrence is 43 years old. Generally normal, sometimes discrete changes in sensory conduction or H-reflex detected GQ1b, GT1a

Other diagnostic entities are often included in the spectrum of Guillain–Barré syndrome. Bickerstaff's brainstem encephalitis, for instance, is part of the group of conditions now regarded as forms of Miller Fisher syndrome (anti-GQ1b antibody syndrome), as well as a related condition labelled "acute ataxic hypersomnolence" where coordination problems and drowsiness are present but no muscle weakness can be detected. BBE is characterized by the rapid onset of ophthalmoplegia, ataxia, and disturbance of consciousness, and may be associated with absent or decreased tendon reflexes and as well as Babinski's sign. The course of the disease is usually monophasic, but recurrent episodes have been reported. MRI abnormalities in the brainstem have been reported in 11%.

Whether isolated acute sensory loss can be regarded as a form of Guillain–Barré syndrome is a matter of dispute; this is a rare occurrence compared to GBS with muscle weakness but no sensory symptoms.

Treatment

Immunotherapy

Plasmapheresis and intravenous immunoglobulins (IVIG) are the two main immunotherapy treatments for GBS. Plasmapheresis attempts to reduce the body's attack on the nervous system by filtering antibodies out of the bloodstream. Similarly, administration of IVIG neutralizes harmful antibodies and inflammation. These two treatments are equally effective, but a combination of the two is not significantly better than either alone. Plasmapheresis speeds recovery when used within four weeks of the onset of symptoms. IVIG works as well as plasmapheresis when started within two weeks of the onset of symptoms, and has fewer complications. IVIG is usually used first because of its ease of administration and safety. Its use is not without risk; occasionally it causes liver inflammation, or in rare cases, kidney failure. Glucocorticoids alone have not been found to be effective in speeding recovery and could potentially delay recovery.

Respiratory failure

Respiratory failure may require intubation of the trachea and breathing support through mechanical ventilation, generally on an intensive care unit. The need for ventilatory support can be anticipated by measurement of two spirometry-based breathing tests: the forced vital capacity (FVC) and the negative inspiratory force (NIF). An FVC of less than 15 ml per kilogram body weight or an NIF of less than 60 cmH2O are considered markers of severe respiratory failure.

Pain

While pain is common in people with Guillain–Barré syndrome, studies comparing different types of pain medication are insufficient to make a recommendation as to which should be used.

Rehabilitation

Following the acute phase, around 40% of people require intensive rehabilitation with the help of a multidisciplinary team to focus on improving activities of daily living (ADLs). Studies into the subject have been limited, but it is likely that intensive rehabilitation improves long-term symptoms. Teams may include physical therapists, occupational therapists, speech language pathologists, social workers, psychologists, other allied health professionals and nurses. The team usually works under the supervision of a neurologist or rehabilitation physician directing treatment goals.

Physiotherapy interventions include strength, endurance and gait training with graduated increases in mobility, maintenance of posture and alignment as well as joint function. Occupational therapy aims to improve everyday function with domestic and community tasks as well as driving and work. Home modifications, gait aids, orthotics and splints may be provided. Speech-language pathology input may be required in those with speech and swallowing problems, as well as to support communication in those who require ongoing breathing support (often through a tracheostomy). Nutritional support may be provided by the team and by dietitians. Psychologists may provide counseling and support. Psychological interventions may also be required for anxiety, fear and depression.

Prognosis

Guillain–Barré syndrome can lead to death as a result of a number of complications: severe infections, blood clots, and cardiac arrest likely due to autonomic neuropathy. Despite optimum care, this occurs in about 5% of cases.

There is a variation in the rate and extent of recovery. The prognosis of Guillain–Barré syndrome is determined mainly by age (those over 40 may have a poorer outcome), and by the severity of symptoms after two weeks. Furthermore, those who experienced diarrhea before the onset of disease have a worse prognosis. On the nerve conduction study, the presence of conduction block predicts poorer outcome at 6 months. In those who have received intravenous immunoglobulins, a smaller increase in IgG in the blood two weeks after administration is associated with poorer mobility outcomes at six months than those whose IgG level increased substantially. If the disease continues to progress beyond four weeks, or there are multiple fluctuations in the severity (more than two in eight weeks), the diagnosis may be chronic inflammatory demyelinating polyneuropathy, which is treated differently.

In research studies, the outcome from an episode of Guillain–Barré syndrome is recorded on a scale from 0 to 6, where 0 denotes completely healthy; 1 very minor symptoms but able to run; 2 able to walk but not to run; 3 requiring a stick or other support; 4 confined to bed or chair; 5 requiring long-term respiratory support; 6 death.

The health-related quality of life (HRQL) after an attack of Guillain–Barré syndrome can be significantly impaired. About a fifth are unable to walk unaided after six months, and many experience chronic pain, fatigue and difficulty with work, education, hobbies and social activities. HRQL improves significantly in the first year.

Epidemiology

In Western countries, the number of new episodes per year has been estimated to be between 0.89 and 1.89 cases per 100,000 people. Children and young adults are less likely to be affected than the elderly: the risk increases by 20% for every decade of life. Men are more likely to develop Guillain–Barré syndrome than women; the relative risk for men is 1.78 compared to women.

The distribution of subtypes varies between countries. In Europe and the United States, 60–80% of people with Guillain–Barré syndrome have the demyelinating subtype (AIDP), and AMAN affects only a small number (6–7%). In Asia and Central and South America, that proportion is significantly higher (30–65%). This may be related to the exposure to different kinds of infection, but also the genetic characteristics of that population. Miller Fisher variant is thought to be more common in Southeast Asia.

History

Georges Guillain, together with Barré and Strohl, described two cases of self-limiting acute paralysis with peculiar changes in the cerebrospinal fluid. He succeeded his teacher Pierre Marie as professor of neurology at the Salpêtrière hospital in Paris in 1925.
 
French physician Jean-Baptiste Octave Landry first described the disorder in 1859. In 1916, Georges Guillain, Jean Alexandre Barré, and André Strohl diagnosed two soldiers with the illness and described the key diagnostic abnormality—albuminocytological dissociation—of increased spinal fluid protein concentration but a normal cell count.

Canadian neurologist C. Miller Fisher described the variant that bears his name in 1956. British neurologist Edwin Bickerstaff, based in Birmingham, described the brainstem encephalitis type in 1951 with Philip Cloake, and made further contributions with another paper in 1957. Guillain had reported on some of these features prior to their full description in 1938. Further subtypes have been described since then, such as the form featuring pure ataxia and the type causing pharyngeal-cervical-brachial weakness. The axonal subtype was first described in the 1990s.

Diagnostic criteria were developed in the late 1970s after the series of cases associated with swine flu vaccination. These were refined in 1990. The case definition was revised by the Brighton Collaboration for vaccine safety in 2009, but is mainly intended for research. Plasma exchange was first used in 1978 and its benefit confirmed in larger studies in 1985. Intravenous immunoglobulins were introduced in 1988, and its non-inferiority compared to plasma exchange was demonstrated in studies in the early 1990s.

Research directions

The understanding of the disease mechanism of Guillain–Barré syndrome has evolved in recent years. Development of new treatments has been limited since immunotherapy was introduced in the 1980s and 1990s. Current research is aimed at demonstrating whether some people who have received IVIg might benefit from a second course if the antibody levels measured in blood after treatment have shown only a small increase. Studies of the immunosuppressive drugs mycophenolate mofetil, brain-derived neurotrophic factor and interferon beta (IFN-β) have not demonstrated benefit to support their widespread use.

An animal model (experimental autoimmune neuritis in rats) is often used for studies, and some agents have shown promise: glatiramer acetate, quinpramine, fasudil (an inhibitor of the Rho-kinase enzyme), and the heart drug flecainide. An antibody targeted against the anti-GD3 antiganglioside antibody has shown benefit in laboratory research. Given the role of the complement system in GBS, it has been suggested that complement inhibitors (such as the drug eculizumab) may be effective.

Inequality (mathematics)

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